Advertisement

Cellular and Molecular Life Sciences

, Volume 76, Issue 9, pp 1641–1652 | Cite as

Intricate role of mitochondrial lipid in mitophagy and mitochondrial apoptosis: its implication in cancer therapeutics

  • Prakash P. Praharaj
  • Prajna P. Naik
  • Debasna P. Panigrahi
  • Chandra S. Bhol
  • Kewal K. Mahapatra
  • Srimanta Patra
  • Gautam Sethi
  • Sujit Kumar BhutiaEmail author
Review
  • 500 Downloads

Abstract

The efficacy of chemotherapy is mostly restricted by the drug resistance developed during the course of cancer treatment. Mitophagy, as a pro-survival mechanism, crucially maintains mitochondrial homeostasis and it is one of the mechanisms that cancer cells adopt for their progression. On the other hand, mitochondrial apoptosis, a precisely regulated form of cell death, acts as a tumor-suppressive mechanism by targeting cancer cells. Mitochondrial lipids, such as cardiolipin, ceramide, and sphingosine-1-phosphate, act as a mitophageal signal for the clearance of damaged mitochondria by interacting with mitophagic machinery as well as activate mitochondrial apoptosis via the release of cytochrome c into the cytoplasm. In the recent time, the lipid-mediated lethal mitophagy has also been used as an alternative approach to abolish the survival role of lipid in cancer. Therefore, by targeting mitochondrial lipids in cancer cells, the detailed mechanism linked to drug resistance can be unraveled. In this review, we precisely discuss the current knowledge about the multifaceted role of mitochondrial lipid in regulating mitophagy and mitochondrial apoptosis and its application in effective cancer therapy.

Keywords

Cardiolipin Ceramide Sphingosine-1-phosphate Mitophagy Mitochondrial apoptosis Cancer therapy 

Notes

Acknowledgements

Research support was partly provided by Department of Biotechnology (Grant number BT/PR7791/BRB/10/1187/2013); Science and Technology Department, Government of Odisha; the Board of Research in Nuclear Sciences (BRNS) (number 37(1)/14/38/2016-BRNS/37276), Department of Atomic Energy (DAE); Science and Engineering Research Board (SERB) (number EMR/2016/001246), Department of Science and Technology.

Compliance with ethical standards

Conflict of interest

The authors disclose no conflict of interest.

References

  1. 1.
    Taylor RW, Turnbull DM (2005) Mitochondrial DNA mutations in human disease. Nat Rev Genet 6:389–402CrossRefPubMedPubMedCentralGoogle Scholar
  2. 2.
    Kang D, Hamasaki N (2005) Alterations of mitochondrial DNA in common diseases and disease states: aging, neurodegeneration, heart failure, diabetes, and cancer. Curr Med Chem 12:429–441CrossRefPubMedGoogle Scholar
  3. 3.
    Horvath SE, Daum G (2013) Lipids of mitochondria. Prog Lipid Res 52:590–614CrossRefPubMedGoogle Scholar
  4. 4.
    van Meer G, Voelker DR, Feigenson GW (2008) Membrane lipids: where they are and how they behave. Nat Rev Mol Cell Biol 9:112–124CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    Vance JE (2015) Phospholipid synthesis and transport in mammalian cells. Traffic (Cph, Den) 16:1–18CrossRefGoogle Scholar
  6. 6.
    Fahy E, Subramaniam S, Murphy RC, Nishijima M, Raetz CR, Shimizu T, Spener F, van Meer G, Wakelam MJ, Dennis EA (2009) Update of the LIPID MAPS comprehensive classification system for lipids. J Lipid Res 50(Suppl):S9–S14CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Campello S, Strappazzon F, Cecconi F (2014) Mitochondrial dismissal in mammals, from protein degradation to mitophagy. Biochem Biophys Acta 1837:451–460PubMedGoogle Scholar
  8. 8.
    Ashrafi G, Schwarz TL (2013) The pathways of mitophagy for quality control and clearance of mitochondria. Cell Death Differ 20:31–42CrossRefPubMedGoogle Scholar
  9. 9.
    Narendra D, Tanaka A, Suen DF, Youle RJ (2008) Parkin is recruited selectively to impaired mitochondria and promotes their autophagy. J Cell Biol 183:795–803CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Meissner C, Lorenz H, Hehn B, Lemberg MK (2015) Intramembrane protease PARL defines a negative regulator of PINK1- and PARK2/Parkin-dependent mitophagy. Autophagy 11:1484–1498CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Jin SM, Lazarou M, Wang C, Kane LA, Narendra DP, Youle RJ (2010) Mitochondrial membrane potential regulates PINK1 import and proteolytic destabilization by PARL. J Cell Biol 191:933–942CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Yamano K, Youle RJ (2013) PINK1 is degraded through the N-end rule pathway. Autophagy 9:1758–1769CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    Kane LA, Lazarou M, Fogel AI, Li Y, Yamano K, Sarraf SA, Banerjee S, Youle RJ (2014) PINK1 phosphorylates ubiquitin to activate Parkin E3 ubiquitin ligase activity. J Cell Biol 205:143–153CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    Koyano F, Okatsu K, Kosako H, Tamura Y, Go E, Kimura M, Kimura Y, Tsuchiya H, Yoshihara H, Hirokawa T, Endo T, Fon EA, Trempe JF, Saeki Y, Tanaka K, Matsuda N (2014) Ubiquitin is phosphorylated by PINK1 to activate parkin. Nature 510:162–166CrossRefPubMedGoogle Scholar
  15. 15.
    Klionsky DJ, Abdelmohsen K, Abe A, Abedin MJ, Abeliovich H, Acevedo Arozena A, Adachi H, Adams CM, Adams PD, Adeli K, Adhihetty PJ, Adler SG, Agam G, Agarwal R, Aghi MK, Agnello M, Agostinis P, Aguilar PV, Aguirre-Ghiso J, Airoldi EM, Ait-Si-Ali S, Akematsu T, Akporiaye ET, Al-Rubeai M, Albaiceta GM, Albanese C, Albani D, Albert ML, Aldudo J, Algul H, Alirezaei M, Alloza I, Almasan A, Almonte-Beceril M, Alnemri ES, Alonso C, Altan-Bonnet N, Altieri DC, Alvarez S, Alvarez-Erviti L, Alves S, Amadoro G, Amano A, Amantini C, Ambrosio S, Amelio I, Amer AO, Amessou M, Amon A, An Z, Anania FA, Andersen SU, Andley UP, Andreadi CK, Andrieu-Abadie N, Anel A, Ann DK, Anoopkumar-Dukie S, Antonioli M, Aoki H, Apostolova N, Aquila S, Aquilano K, Araki K, Arama E, Aranda A, Araya J, Arcaro A, Arias E, Arimoto H, Ariosa AR, Armstrong JL, Arnould T, Arsov I, Asanuma K, Askanas V, Asselin E, Atarashi R, Atherton SS, Atkin JD, Attardi LD, Auberger P, Auburger G, Aurelian L, Autelli R, Avagliano L, Avantaggiati ML, Avrahami L, Awale S, Azad N, Bachetti T, Backer JM, Bae DH, Bae JS, Bae ON, Bae SH, Baehrecke EH, Baek SH, Baghdiguian S, Bagniewska-Zadworna A et al (2016) Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition). Autophagy 12:1–222CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    Birgisdottir AB, Lamark T, Johansen T (2013) The LIR motif—crucial for selective autophagy. J Cell Sci 126:3237–3247PubMedGoogle Scholar
  17. 17.
    Novak I, Kirkin V, McEwan DG, Zhang J, Wild P, Rozenknop A, Rogov V, Lohr F, Popovic D, Occhipinti A, Reichert AS, Terzic J, Dotsch V, Ney PA, Dikic I (2010) Nix is a selective autophagy receptor for mitochondrial clearance. EMBO Rep 11:45–51CrossRefPubMedGoogle Scholar
  18. 18.
    Quinsay MN, Thomas RL, Lee Y, Gustafsson AB (2010) Bnip3-mediated mitochondrial autophagy is independent of the mitochondrial permeability transition pore. Autophagy 6:855–862CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    Liu L, Feng D, Chen G, Chen M, Zheng Q, Song P, Ma Q, Zhu C, Wang R, Qi W, Huang L, Xue P, Li B, Wang X, Jin H, Wang J, Yang F, Liu P, Zhu Y, Sui S, Chen Q (2012) Mitochondrial outer-membrane protein FUNDC1 mediates hypoxia-induced mitophagy in mammalian cells. Nat Cell Biol 14:177–185CrossRefPubMedGoogle Scholar
  20. 20.
    Strappazzon F, Nazio F, Corrado M, Cianfanelli V, Romagnoli A, Fimia GM, Campello S, Nardacci R, Piacentini M, Campanella M, Cecconi F (2015) AMBRA1 is able to induce mitophagy via LC3 binding, regardless of PARKIN and p62/SQSTM1. Cell Death Differ 22:419–432CrossRefPubMedGoogle Scholar
  21. 21.
    Murakawa T, Yamaguchi O, Hashimoto A, Hikoso S, Takeda T, Oka T, Yasui H, Ueda H, Akazawa Y, Nakayama H, Taneike M, Misaka T, Omiya S, Shah AM, Yamamoto A, Nishida K, Ohsumi Y, Okamoto K, Sakata Y, Otsu K (2015) Bcl-2-like protein 13 is a mammalian Atg32 homologue that mediates mitophagy and mitochondrial fragmentation. Nat Commun 6:7527CrossRefPubMedPubMedCentralGoogle Scholar
  22. 22.
    Rambold AS, Kostelecky B, Elia N, Lippincott-Schwartz J (2011) Tubular network formation protects mitochondria from autophagosomal degradation during nutrient starvation. Proc Natl Acad Sci USA 108:10190–10195CrossRefPubMedGoogle Scholar
  23. 23.
    Galluzzi L, Vitale I, Aaronson SA, Abrams JM, Adam D, Agostinis P, Alnemri ES, Altucci L, Amelio I, Andrews DW, Annicchiarico-Petruzzelli M, Antonov AV, Arama E, Baehrecke EH, Barlev NA, Bazan NG, Bernassola F, Bertrand MJM, Bianchi K, Blagosklonny MV, Blomgren K, Borner C, Boya P, Brenner C, Campanella M, Candi E, Carmona-Gutierrez D, Cecconi F, Chan FK, Chandel NS, Cheng EH, Chipuk JE, Cidlowski JA, Ciechanover A, Cohen GM, Conrad M, Cubillos-Ruiz JR, Czabotar PE, D’Angiolella V, Dawson TM, De Dawson VL, Laurenzi V De, Maria R, Debatin KM, DeBerardinis RJ, Deshmukh M Di, Daniele N Di, Virgilio F, Dixit VM, Dixon SJ, Duckett CS, Dynlacht BD, El-Deiry WS, Elrod JW, Fimia GM, Fulda S, Garcia-Saez AJ, Garg AD, Garrido C, Gavathiotis E, Golstein P, Gottlieb E, Green DR, Greene LA, Gronemeyer H, Gross A, Hajnoczky G, Hardwick JM, Harris IS, Hengartner MO, Hetz C, Ichijo H, Jaattela M, Joseph B, Jost PJ, Juin PP, Kaiser WJ, Karin M, Kaufmann T, Kepp O, Kimchi A, Kitsis RN, Klionsky DJ, Knight RA, Kumar S, Lee SW, Lemasters JJ, Levine B, Linkermann A, Lipton SA, Lockshin RA, Lopez-Otin C, Lowe SW, Luedde T, Lugli E, MacFarlane M, Madeo F, Malewicz M, Malorni W, Manic G et al (2018) Molecular mechanisms of cell death: recommendations of the Nomenclature Committee on Cell Death 2018. Cell Death Differ 25:486–541CrossRefPubMedPubMedCentralGoogle Scholar
  24. 24.
    Ott M, Zhivotovsky B, Orrenius S (2007) Role of cardiolipin in cytochrome c release from mitochondria. Cell Death Differ 14:1243–1247CrossRefPubMedGoogle Scholar
  25. 25.
    Tait SW, Green DR (2010) Mitochondria and cell death: outer membrane permeabilization and beyond. Nat Rev Mol Cell Biol 11:621–632CrossRefPubMedGoogle Scholar
  26. 26.
    Zaman S, Wang R, Gandhi V (2014) Targeting the apoptosis pathway in hematologic malignancies. Leuk Lymphoma 55:1980–1992CrossRefPubMedPubMedCentralGoogle Scholar
  27. 27.
    Lopez J, Tait SW (2015) Mitochondrial apoptosis: killing cancer using the enemy within. Br J Cancer 112:957–962CrossRefPubMedPubMedCentralGoogle Scholar
  28. 28.
    Schlattner U, Tokarska-Schlattner M, Rousseau D, Boissan M, Mannella C, Epand R, Lacombe ML (2014) Mitochondrial cardiolipin/phospholipid trafficking: the role of membrane contact site complexes and lipid transfer proteins. Chem Phys Lipid 179:32–41CrossRefGoogle Scholar
  29. 29.
    Houtkooper RH, Akbari H, van Lenthe H, Kulik W, Wanders RJ, Frentzen M, Vaz FM (2006) Identification and characterization of human cardiolipin synthase. FEBS Lett 580:3059–3064CrossRefPubMedGoogle Scholar
  30. 30.
    Arnarez C, Marrink SJ, Periole X (2013) Identification of cardiolipin binding sites on cytochrome c oxidase at the entrance of proton channels. Sci Rep 3:1263CrossRefPubMedPubMedCentralGoogle Scholar
  31. 31.
    Sharpley MS, Shannon RJ, Draghi F, Hirst J (2006) Interactions between phospholipids and NADH:ubiquinone oxidoreductase (complex I) from bovine mitochondria. Biochemistry 45:241–248CrossRefPubMedGoogle Scholar
  32. 32.
    Sinibaldi F, Howes BD, Droghetti E, Polticelli F, Piro MC, Di Pierro D, Fiorucci L, Coletta M, Smulevich G, Santucci R (2013) Role of lysines in cytochrome c-cardiolipin interaction. Biochemistry 52:4578–4588CrossRefPubMedGoogle Scholar
  33. 33.
    Khalifat N, Fournier JB, Angelova MI, Puff N (2011) Lipid packing variations induced by pH in cardiolipin-containing bilayers: the driving force for the cristae-like shape instability. Biochem Biophys Acta 1808:2724–2733CrossRefPubMedGoogle Scholar
  34. 34.
    Chu CT, Ji J, Dagda RK, Jiang JF, Tyurina YY, Kapralov AA, Tyurin VA, Yanamala N, Shrivastava IH, Mohammadyani D, Wang KZQ, Zhu J, Klein-Seetharaman J, Balasubramanian K, Amoscato AA, Borisenko G, Huang Z, Gusdon AM, Cheikhi A, Steer EK, Wang R, Baty C, Watkins S, Bahar I, Bayir H, Kagan VE (2013) Cardiolipin externalization to the outer mitochondrial membrane acts as an elimination signal for mitophagy in neuronal cells. Nat Cell Biol 15:1197–1205CrossRefPubMedPubMedCentralGoogle Scholar
  35. 35.
    Kagan VE, Jiang J, Huang Z, Tyurina YY, Desbourdes C, Cottet-Rousselle C, Dar HH, Verma M, Tyurin VA, Kapralov AA, Cheikhi A, Mao G, Stolz D, St Croix CM, Watkins S, Shen Z, Li Y, Greenberg ML, Tokarska-Schlattner M, Boissan M, Lacombe ML, Epand RM, Chu CT, Mallampalli RK, Bayir H, Schlattner U (2016) NDPK-D (NM23-H4)-mediated externalization of cardiolipin enables elimination of depolarized mitochondria by mitophagy. Cell Death Differ 23:1140–1151CrossRefPubMedPubMedCentralGoogle Scholar
  36. 36.
    Ren M, Phoon CK, Schlame M (2014) Metabolism and function of mitochondrial cardiolipin. Prog Lipid Res 55:1–16CrossRefPubMedGoogle Scholar
  37. 37.
    Chu CT, Bayir H, Kagan VE (2014) LC3 binds externalized cardiolipin on injured mitochondria to signal mitophagy in neurons: implications for Parkinson disease. Autophagy 10:376–378CrossRefPubMedGoogle Scholar
  38. 38.
    Hsu P, Liu X, Zhang J, Wang HG, Ye JM, Shi Y (2015) Cardiolipin remodeling by TAZ/tafazzin is selectively required for the initiation of mitophagy. Autophagy 11:643–652CrossRefPubMedPubMedCentralGoogle Scholar
  39. 39.
    Anton Z, Landajuela A, Hervas JH, Montes LR, Hernandez-Tiedra S, Velasco G, Goni FM, Alonso A (2016) Human Atg8-cardiolipin interactions in mitophagy: specific properties of LC3B, GABARAPL2 and GABARAP. Autophagy 12:2386–2403CrossRefPubMedPubMedCentralGoogle Scholar
  40. 40.
    Shen Z, Li Y, Gasparski AN, Abeliovich H, Greenberg ML (2017) Cardiolipin regulates mitophagy through the protein kinase C pathway. J Biol Chem 292:2916–2923CrossRefPubMedPubMedCentralGoogle Scholar
  41. 41.
    Shimasaki K, Watanabe-Takahashi M, Umeda M, Funamoto S, Saito Y, Noguchi N, Kumagai K, Hanada K, Tsukahara F, Maru Y, Shibata N, Naito M, Nishikawa K (2018) Pleckstrin homology domain of p210 BCR-ABL interacts with cardiolipin to regulate its mitochondrial translocation and subsequent mitophagy. Genes Cells Devoted Mol Cell Mech 23:22–34CrossRefGoogle Scholar
  42. 42.
    Hernandez-Corbacho MJ, Canals D, Adada MM, Liu M, Senkal CE, Yi JK, Mao C, Luberto C, Hannun YA, Obeid LM (2015) Tumor necrosis factor-alpha (TNFalpha)-induced ceramide generation via ceramide synthases regulates loss of focal adhesion kinase (FAK) and programmed cell death. J Biol Chem 290:25356–25373CrossRefPubMedPubMedCentralGoogle Scholar
  43. 43.
    Mullen TD, Hannun YA, Obeid LM (2012) Ceramide synthases at the centre of sphingolipid metabolism and biology. Biochem J 441:789–802CrossRefPubMedPubMedCentralGoogle Scholar
  44. 44.
    Novgorodov SA, Wu BX, Gudz TI, Bielawski J, Ovchinnikova TV, Hannun YA, Obeid LM (2011) Novel pathway of ceramide production in mitochondria: thioesterase and neutral ceramidase produce ceramide from sphingosine and acyl-CoA. J Biol Chem 286:25352–25362CrossRefPubMedPubMedCentralGoogle Scholar
  45. 45.
    Novgorodov SA, Chudakova DA, Wheeler BW, Bielawski J, Kindy MS, Obeid LM, Gudz TI (2011) Developmentally regulated ceramide synthase 6 increases mitochondrial Ca2+ loading capacity and promotes apoptosis. J Biol Chem 286:4644–4658CrossRefPubMedGoogle Scholar
  46. 46.
    Sentelle RD, Senkal CE, Jiang W, Ponnusamy S, Gencer S, Selvam SP, Ramshesh VK, Peterson YK, Lemasters JJ, Szulc ZM, Bielawski J, Ogretmen B (2012) Ceramide targets autophagosomes to mitochondria and induces lethal mitophagy. Nat Chem Biol 8:831–838CrossRefPubMedPubMedCentralGoogle Scholar
  47. 47.
    Dany M, Gencer S, Nganga R, Thomas RJ, Oleinik N, Baron KD, Szulc ZM, Ruvolo P, Kornblau S, Andreeff M, Ogretmen B (2016) Targeting FLT3-ITD signaling mediates ceramide-dependent mitophagy and attenuates drug resistance in AML. Blood 128:1944–1958CrossRefPubMedPubMedCentralGoogle Scholar
  48. 48.
    Panda PK, Naik PP, Meher BR, Das DN, Mukhopadhyay S, Praharaj PP, Maiti TK, Bhutia SK (2018) PUMA dependent mitophagy by Abrus agglutinin contributes to apoptosis through ceramide generation. Biochem Biophys Acta 1865:480–495CrossRefGoogle Scholar
  49. 49.
    Maceyka M, Harikumar KB, Milstien S, Spiegel S (2012) Sphingosine-1-phosphate signaling and its role in disease. Trends Cell Biol 22:50–60CrossRefPubMedGoogle Scholar
  50. 50.
    Strub GM, Paillard M, Liang J, Gomez L, Allegood JC, Hait NC, Maceyka M, Price MM, Chen Q, Simpson DC, Kordula T, Milstien S, Lesnefsky EJ, Spiegel S (2011) Sphingosine-1-phosphate produced by sphingosine kinase 2 in mitochondria interacts with prohibitin 2 to regulate complex IV assembly and respiration. FASEB J Off Publ Fed Am Soc Exp Biol 25:600–612Google Scholar
  51. 51.
    Song DD, Zhang TT, Chen JL, Xia YF, Qin ZH, Waeber C, Sheng R (2017) Sphingosine kinase 2 activates autophagy and protects neurons against ischemic injury through interaction with Bcl-2 via its putative BH3 domain. Cell Death Dis 8:e2912CrossRefPubMedPubMedCentralGoogle Scholar
  52. 52.
    Wei Y, Chiang WC, Sumpter R Jr, Mishra P, Levine B (2017) Prohibitin 2 is an inner mitochondrial membrane mitophagy receptor. Cell 168:224–238.e10CrossRefPubMedGoogle Scholar
  53. 53.
    Mitroi DN, Karunakaran I, Graler M, Saba JD, Ehninger D, Ledesma MD, van Echten-Deckert G (2017) SGPL1 (sphingosine phosphate lyase 1) modulates neuronal autophagy via phosphatidylethanolamine production. Autophagy 13:885–899CrossRefPubMedPubMedCentralGoogle Scholar
  54. 54.
    Haines TH, Dencher NA (2002) Cardiolipin: a proton trap for oxidative phosphorylation. FEBS Lett 528:35–39CrossRefPubMedGoogle Scholar
  55. 55.
    Huttemann M, Pecina P, Rainbolt M, Sanderson TH, Kagan VE, Samavati L, Doan JW, Lee I (2011) The multiple functions of cytochrome c and their regulation in life and death decisions of the mammalian cell: from respiration to apoptosis. Mitochondrion 11:369–381CrossRefPubMedPubMedCentralGoogle Scholar
  56. 56.
    Belikova NA, Vladimirov YA, Osipov AN, Kapralov AA, Tyurin VA, Potapovich MV, Basova LV, Peterson J, Kurnikov IV, Kagan VE (2006) Peroxidase activity and structural transitions of cytochrome c bound to cardiolipin-containing membranes. Biochemistry 45:4998–5009CrossRefPubMedPubMedCentralGoogle Scholar
  57. 57.
    Min L, Jian-xing X (2007) Detoxifying function of cytochrome c against oxygen toxicity. Mitochondrion 7:13–16CrossRefPubMedGoogle Scholar
  58. 58.
    Zhang T, Saghatelian A (2013) Emerging roles of lipids in BCL-2 family-regulated apoptosis. Biochem Biophys Acta 1831:1542–1554PubMedGoogle Scholar
  59. 59.
    Raemy E, Martinou JC (2014) Involvement of cardiolipin in tBID-induced activation of BAX during apoptosis. Chem Phys Lipid 179:70–74CrossRefGoogle Scholar
  60. 60.
    Shamas-Din A, Bindner S, Zhu W, Zaltsman Y, Campbell C, Gross A, Leber B, Andrews DW, Fradin C (2013) tBid undergoes multiple conformational changes at the membrane required for Bax activation. J Biol Chem 288:22111–22127CrossRefPubMedPubMedCentralGoogle Scholar
  61. 61.
    Caroppi P, Sinibaldi F, Fiorucci L, Santucci R (2009) Apoptosis and human diseases: mitochondrion damage and lethal role of released cytochrome C as proapoptotic protein. Curr Med Chem 16:4058–4065CrossRefPubMedGoogle Scholar
  62. 62.
    Lai YC, Li CC, Sung TC, Chang CW, Lan YJ, Chiang YW (2019) The role of cardiolipin in promoting the membrane pore-forming activity of BAX oligomers. Biochim Biophys Acta Biomembr 1861:268–280Google Scholar
  63. 63.
    Deng X, Yin X, Allan R, Lu DD, Maurer CW, Haimovitz-Friedman A, Fuks Z, Shaham S, Kolesnick R (2008) Ceramide biogenesis is required for radiation-induced apoptosis in the germ line of C. elegans. Science (New York, NY) 322:110–115CrossRefGoogle Scholar
  64. 64.
    Birbes H, Luberto C, Hsu YT, El Bawab S, Hannun YA, Obeid LM (2005) A mitochondrial pool of sphingomyelin is involved in TNFalpha-induced Bax translocation to mitochondria. Biochem J 386:445–451CrossRefPubMedPubMedCentralGoogle Scholar
  65. 65.
    Birbes H, El Bawab S, Hannun YA, Obeid LM (2001) Selective hydrolysis of a mitochondrial pool of sphingomyelin induces apoptosis. FASEB J Off Publ Fed Am Soc Exp Biol 15:2669–2679Google Scholar
  66. 66.
    Ogretmen B, Hannun YA (2004) Biologically active sphingolipids in cancer pathogenesis and treatment. Nat Rev Cancer 4:604–616CrossRefPubMedGoogle Scholar
  67. 67.
    Ganesan V, Perera MN, Colombini D, Datskovskiy D, Chadha K, Colombini M (2010) Ceramide and activated Bax act synergistically to permeabilize the mitochondrial outer membrane. Apoptosis Int J Programmed Cell Death 15:553–562CrossRefGoogle Scholar
  68. 68.
    Stiban J, Caputo L, Colombini M (2008) Ceramide synthesis in the endoplasmic reticulum can permeabilize mitochondria to proapoptotic proteins. J Lipid Res 49:625–634CrossRefPubMedGoogle Scholar
  69. 69.
    Jain A, Beutel O, Ebell K, Korneev S, Holthuis JC (2017) Diverting CERT-mediated ceramide transport to mitochondria triggers Bax-dependent apoptosis. J Cell Sci 130:360–371CrossRefPubMedGoogle Scholar
  70. 70.
    Sawada M, Nakashima S, Banno Y, Yamakawa H, Takenaka K, Shinoda J, Nishimura Y, Sakai N, Nozawa Y (2000) Influence of Bax or Bcl-2 overexpression on the ceramide-dependent apoptotic pathway in glioma cells. Oncogene 19:3508–3520CrossRefPubMedGoogle Scholar
  71. 71.
    Yabu T, Shiba H, Shibasaki Y, Nakanishi T, Imamura S, Touhata K, Yamashita M (2015) Stress-induced ceramide generation and apoptosis via the phosphorylation and activation of nSMase1 by JNK signaling. Cell Death Differ 22:258–273CrossRefPubMedGoogle Scholar
  72. 72.
    Siskind LJ, Feinstein L, Yu T, Davis JS, Jones D, Choi J, Zuckerman JE, Tan W, Hill RB, Hardwick JM, Colombini M (2008) Anti-apoptotic Bcl-2 family proteins disassemble ceramide channels. J Biol Chem 283:6622–6630CrossRefPubMedPubMedCentralGoogle Scholar
  73. 73.
    Lee H, Rotolo JA, Mesicek J, Penate-Medina T, Rimner A, Liao WC, Yin X, Ragupathi G, Ehleiter D, Gulbins E, Zhai D, Reed JC, Haimovitz-Friedman A, Fuks Z, Kolesnick R (2011) Mitochondrial ceramide-rich macrodomains functionalize Bax upon irradiation. PLoS One 6:e19783CrossRefPubMedPubMedCentralGoogle Scholar
  74. 74.
    Kim HJ, Oh JE, Kim SW, Chun YJ, Kim MY (2008) Ceramide induces p38 MAPK-dependent apoptosis and Bax translocation via inhibition of Akt in HL-60 cells. Cancer Lett 260:88–95CrossRefPubMedGoogle Scholar
  75. 75.
    Beverly LJ, Howell LA, Hernandez-Corbacho M, Casson L, Chipuk JE, Siskind LJ (2013) BAK activation is necessary and sufficient to drive ceramide synthase-dependent ceramide accumulation following inhibition of BCL2-like proteins. Biochem J 452:111–119CrossRefPubMedPubMedCentralGoogle Scholar
  76. 76.
    Ohta H, Yatomi Y, Sweeney EA, Hakomori S, Igarashi Y (1994) A possible role of sphingosine in induction of apoptosis by tumor necrosis factor-alpha in human neutrophils. FEBS Lett 355:267–270CrossRefPubMedGoogle Scholar
  77. 77.
    Cuvillier O, Edsall L, Spiegel S (2000) Involvement of sphingosine in mitochondria-dependent Fas-induced apoptosis of type II Jurkat T cells. J Biol Chem 275:15691–15700CrossRefPubMedGoogle Scholar
  78. 78.
    Chipuk JE, McStay GP, Bharti A, Kuwana T, Clarke CJ, Siskind LJ, Obeid LM, Green DR (2012) Sphingolipid metabolism cooperates with BAK and BAX to promote the mitochondrial pathway of apoptosis. Cell 148:988–1000CrossRefPubMedPubMedCentralGoogle Scholar
  79. 79.
    Liu H, Toman RE, Goparaju SK, Maceyka M, Nava VE, Sankala H, Payne SG, Bektas M, Ishii I, Chun J, Milstien S, Spiegel S (2003) Sphingosine kinase type 2 is a putative BH3-only protein that induces apoptosis. J Biol Chem 278:40330–40336CrossRefPubMedGoogle Scholar
  80. 80.
    Nagahashi M, Tsuchida J, Moro K, Hasegawa M, Tatsuda K, Woelfel IA, Takabe K, Wakai T (2016) High levels of sphingolipids in human breast cancer. J Surg Res 204:435–444CrossRefPubMedPubMedCentralGoogle Scholar
  81. 81.
    Zhang L, Liu X, Zuo Z, Hao C, Ma Y (2016) Sphingosine kinase 2 promotes colorectal cancer cell proliferation and invasion by enhancing MYC expression. Tumour Biol J Int Soc Oncodev Biol Med 37:8455–8460CrossRefGoogle Scholar
  82. 82.
    Venant H, Rahmaniyan M, Jones EE, Lu P, Lilly MB, Garrett-Mayer E, Drake RR, Kraveka JM, Smith CD, Voelkel-Johnson C (2015) The sphingosine kinase 2 inhibitor ABC294640 reduces the growth of prostate cancer cells and results in accumulation of dihydroceramides in vitro and in vivo. Mol Cancer Ther 14:2744–2752CrossRefPubMedPubMedCentralGoogle Scholar
  83. 83.
    Holohan C, Van Schaeybroeck S, Longley DB, Johnston PG (2013) Cancer drug resistance: an evolving paradigm. Nat Rev Cancer 13:714–726CrossRefGoogle Scholar
  84. 84.
    Kubli DA, Gustafsson AB (2012) Mitochondria and mitophagy: the yin and yang of cell death control. Circ Res 111:1208–1221CrossRefPubMedPubMedCentralGoogle Scholar
  85. 85.
    Dany M, Ogretmen B (2015) Ceramide induced mitophagy and tumor suppression. Biochem Biophys Acta 1853:2834–2845CrossRefPubMedGoogle Scholar
  86. 86.
    Stein EM, Tallman MS (2016) Emerging therapeutic drugs for AML. Blood 127:71–78CrossRefPubMedPubMedCentralGoogle Scholar
  87. 87.
    Thomas RJ, Oleinik N, Panneer Selvam S, Vaena SG, Dany M, Nganga RN, Depalma R, Baron KD, Kim J, Szulc ZM, Ogretmen B (2017) HPV/E7 induces chemotherapy-mediated tumor suppression by ceramide-dependent mitophagy. EMBO Mol Med 9:1030–1051CrossRefPubMedPubMedCentralGoogle Scholar
  88. 88.
    Guillermet-Guibert J, Davenne L, Pchejetski D, Saint-Laurent N, Brizuela L, Guilbeau-Frugier C, Delisle MB, Cuvillier O, Susini C, Bousquet C (2009) Targeting the sphingolipid metabolism to defeat pancreatic cancer cell resistance to the chemotherapeutic gemcitabine drug. Mol Cancer Ther 8:809–820CrossRefPubMedGoogle Scholar
  89. 89.
    Liu K, Guo TL, Hait NC, Allegood J, Parikh HI, Xu W, Kellogg GE, Grant S, Spiegel S, Zhang S (2013) Biological characterization of 3-(2-amino-ethyl)-5-[3-(4-butoxyl-phenyl)-propylidene]-thiazolidine-2,4-dione (K145) as a selective sphingosine kinase-2 inhibitor and anticancer agent. PLoS One 8:e56471CrossRefPubMedPubMedCentralGoogle Scholar
  90. 90.
    Sankala HM, Hait NC, Paugh SW, Shida D, Lepine S, Elmore LW, Dent P, Milstien S, Spiegel S (2007) Involvement of sphingosine kinase 2 in p53-independent induction of p21 by the chemotherapeutic drug doxorubicin. Cancer Res 67:10466–10474CrossRefPubMedGoogle Scholar
  91. 91.
    Kane RC, Farrell AT, Saber H, Tang S, Williams G, Jee JM, Liang C, Booth B, Chidambaram N, Morse D, Sridhara R, Garvey P, Justice R, Pazdur R (2006) Sorafenib for the treatment of advanced renal cell carcinoma. Clin Cancer Res Off J Am Assoc Cancer Res 12:7271–7278CrossRefGoogle Scholar
  92. 92.
    Tran MA, Smith CD, Kester M, Robertson GP (2008) Combining nanoliposomal ceramide with sorafenib synergistically inhibits melanoma and breast cancer cell survival to decrease tumor development. Clin Cancer Res Off J Am Assoc Cancer Res 14:3571–3581CrossRefGoogle Scholar
  93. 93.
    Britten CD, Garrett-Mayer E, Chin SH, Shirai K, Ogretmen B, Bentz TA, Brisendine A, Anderton K, Cusack SL, Maines LW, Zhuang Y, Smith CD, Thomas MB (2017) A phase I study of ABC294640, a first-in-class sphingosine kinase-2 inhibitor, in patients with advanced solid tumors. Clin Cancer Res Off J Am Assoc Cancer Res 23:4642–4650CrossRefGoogle Scholar
  94. 94.
    Beljanski V, Knaak C, Zhuang Y, Smith CD (2011) Combined anticancer effects of sphingosine kinase inhibitors and sorafenib. Investig New Drugs 29:1132–1142CrossRefGoogle Scholar
  95. 95.
    Min J, Mesika A, Sivaguru M, Van Veldhoven PP, Alexander H, Futerman AH, Alexander S (2007) (Dihydro)ceramide synthase 1 regulated sensitivity to cisplatin is associated with the activation of p38 mitogen-activated protein kinase and is abrogated by sphingosine kinase 1. Mol Cancer Res 5:801–812CrossRefPubMedGoogle Scholar
  96. 96.
    Gouaze-Andersson V, Flowers M, Karimi R, Fabrias G, Delgado A, Casas J, Cabot MC (2011) Inhibition of acid ceramidase by a 2-substituted aminoethanol amide synergistically sensitizes prostate cancer cells to N-(4-hydroxyphenyl) retinamide. Prostate 71:1064–1073CrossRefPubMedGoogle Scholar
  97. 97.
    Flowers M, Fabrias G, Delgado A, Casas J, Abad JL, Cabot MC (2012) C6-ceramide and targeted inhibition of acid ceramidase induce synergistic decreases in breast cancer cell growth. Breast Cancer Res Treat 133:447–458CrossRefPubMedGoogle Scholar
  98. 98.
    Morad SA, Levin JC, Shanmugavelandy SS, Kester M, Fabrias G, Bedia C, Cabot MC (2012) Ceramide–antiestrogen nanoliposomal combinations–novel impact of hormonal therapy in hormone-insensitive breast cancer. Mol Cancer Ther 11:2352–2361CrossRefPubMedPubMedCentralGoogle Scholar
  99. 99.
    Niemi NM, Lanning NJ, Westrate LM, MacKeigan JP (2013) Downregulation of the mitochondrial phosphatase PTPMT1 is sufficient to promote cancer cell death. PLoS One 8:e53803CrossRefPubMedPubMedCentralGoogle Scholar
  100. 100.
    Hockenbery D, Nunez G, Milliman C, Schreiber RD, Korsmeyer SJ (1990) Bcl-2 is an inner mitochondrial membrane protein that blocks programmed cell death. Nature 348:334–336CrossRefPubMedGoogle Scholar
  101. 101.
    Kim SK, Foote MB, Huang L (2012) The targeted intracellular delivery of cytochrome C protein to tumors using lipid-apolipoprotein nanoparticles. Biomaterials 33:3959–3966CrossRefPubMedPubMedCentralGoogle Scholar
  102. 102.
    Mendez J, Morales Cruz M, Delgado Y, Figueroa CM, Orellano EA, Morales M, Monteagudo A, Griebenow K (2014) Delivery of chemically glycosylated cytochrome c immobilized in mesoporous silica nanoparticles induces apoptosis in HeLa cancer cells. Mol Pharm 11:102–111CrossRefPubMedGoogle Scholar
  103. 103.
    Vladimirov YA, Sarisozen C, Vladimirov GK, Filipczak N, Polimova AM, Torchilin VP (2017) The cytotoxic action of cytochrome C/cardiolipin nanocomplex (Cyt-CL) on cancer cells in culture. Pharm Res 34:1264–1275CrossRefPubMedGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2018

Authors and Affiliations

  1. 1.Department of Life ScienceNational Institute of Technology RourkelaRourkelaIndia
  2. 2.PG Department of ZoologyVikram Deb (Auto) CollegeJeyporeIndia
  3. 3.Department of Pharmacology, Yong Loo Lin School of MedicineNational University of SingaporeSingaporeSingapore

Personalised recommendations