Abstract
Peroxisomes are single membrane-bound organelles ubiquitously present in several cell types and are associated with cell and tissue-specific functions. Their role in cellular ageing is under investigation in various model systems. Metabolism of cellular reactive oxygen species is a universal function performed by these organelles. In this study, we investigated alterations in peroxisome number upon early replicative ageing of yeast cells. Increase in the number of peroxisomes in replicatively aged mother cells of wild-type yeast was observed when cultured in both peroxisome-inducing and non-inducing medium. Further, we investigated if this increase in peroxisome number in replicatively aged cells is due to enhanced peroxisome proliferation. For this, the number of peroxisomes in replicatively aged mother cells of pex11, pex25 and pex11pex25 was analysed. Increased percentage of aged cells was observed in pex25 and pex11pex25 cells cultured in peroxisome-inducing oleic acid medium. Interestingly, when cultured in oleic acid, young mother cells devoid of Pex11 showed reduced peroxisome proliferation compared to old mother cells. Induced activity of the antioxidant enzyme catalase and reduced accumulation of reactive oxygen species were reported in all studied strains when cultured in oleic acid medium. Further, our data also suggest that replicatively aged cells with increased peroxisome number also display mitochondrial dysfunction and fragmentation in all the strains studied. In conclusion, our data suggests a correlation between increase in peroxisome number and replicative age of yeast cells and interestingly this increase seems to be partly dependent on the fission proteins.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
Availability of data and material
Not applicable.
Code availability
Not applicable.
References
Ayer A, Gourlay CW, Dawes IW (2014) Cellular redox homeostasis, reactive oxygen species and replicative ageing in Saccharomyces cerevisiae. FEMS Yeast Res 14:60–72. https://doi.org/10.1111/1567-1364.12114
Azbarova AV, Galkina KV, Sorokin MI, Severin FF, Knorre DA (2017) The contribution of Saccharomyces cerevisiae replicative age to the variations in the levels of Trx2p, Pdr5p, Can1p and Idh isoforms. Sci Rep 7:1–10. https://doi.org/10.1038/s41598-017-13576-w
Banerjee R, Joshi N, Nagotu S (2020) Cell organelles and yeast longevity: an intertwined regulation. Curr Genet 66:15–41. https://doi.org/10.1007/s00294-019-01035-0
Bernhardt D, Müller M, Reichert AS, Osiewacz HD (2015) Simultaneous impairment of mitochondrial fission and fusion reduces mitophagy and shortens replicative lifespan. Sci Rep 5:7885. https://doi.org/10.1038/srep07885
Bhattacharya S, Bouklas T, Fries BC (2020) Replicative aging in pathogenic fungi. J Fungi (basel) 7:6. https://doi.org/10.3390/jof7010006
Bradford MM (1976) A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 72:248–254. https://doi.org/10.1006/abio.1976.9999
Chalermwat C, Thosapornvichai T, Jensen LT, Wattanasirichaigoon D (2020) Genetic analysis of peroxisomal genes required for longevity in a yeast model of citrin deficiency. Diseases 8:2. https://doi.org/10.3390/diseases8010002
Chen Y, Liu X, Zhao W, Cui H, Ruan J, Yuan Y, Tu Z (2017) MET18 deficiency increases the sensitivity of yeast to oxidative stress and shortens replicative lifespan by inhibiting catalase activity. BioMed Res Int 2017:7587395. https://doi.org/10.1155/2017/7587395
Cipolla CM, Lodhi IJ (2017) Peroxisomal dysfunction in age-related diseases. Trends Endocrinol Metab 28:297–308. https://doi.org/10.1016/j.tem.2016.12.003
Cohen G, Rapatz W, Ruis H (1988) Sequence of the Saccharomyces cerevisiae CTA1 gene and amino acid sequence of catalase A derived from it. Eur J Biochem 176:159–163. https://doi.org/10.1111/j.1432-1033.1988.tb14263.x
Dang W, Steffen KK, Perry R, Dorsey JA, Johnson FB, Shilatifard A, Kaeberlein M, Kennedy BK, Berger SL (2009) Histone H4 lysine 16 acetylation regulates cellular lifespan. Nature 459:802–807. https://doi.org/10.1038/nature08085
Deb R, Nagotu S (2017) Versatility of peroxisomes: an evolving concept. Tissue Cell 49:209–226. https://doi.org/10.1016/j.tice.2017.03.002
Denoth Lippuner A, Julou T, Barral Y (2014) Budding yeast as a model organism to study the effects of age. FEMS Microbiol Rev 38:300–325. https://doi.org/10.1111/1574-6976.12060
Deori NM, Kale A, Maurya PK, Nagotu S (2018) Peroxisomes: role in cellular ageing and age related disorders. Biogerontology 19:303–324. https://doi.org/10.1007/s10522-018-9761-9
Dhar R, Missarova AM, Lehner B, Carey LB (2019) Single cell functional genomics reveals the importance of mitochondria in cell-to-cell phenotypic variation. Elife 8:e38904. https://doi.org/10.7554/eLife.38904
Epstein CB, Waddle JA, Hale W 4th, Davé V, Thornton J, Macatee TL, Garner HR, Butow RA (2001) Genome-wide responses to mitochondrial dysfunction. Mol Biol Cell 12:297–308. https://doi.org/10.1091/mbc.12.2.297
Erdmann R, Veenhuis M, Mertens D, Kunau WH (1989) Isolation of peroxisome-deficient mutants of Saccharomyces cerevisiae. Proc Natl Acad Sci USA 86:5419–5423. https://doi.org/10.1073/pnas.86.14.5419
Fabrizio P, Longo VD (2003) The chronological life span of Saccharomyces cerevisiae. Aging Cell 2:73–81. https://doi.org/10.1046/j.1474-9728.2003.00033.x
Feser J, Truong D, Das C, Carson JJ, Kieft J, Harkness T, Tyler JK (2010) Elevated histone expression promotes life span extension. Mol Cell 39:724–735. https://doi.org/10.1016/j.molcel.2010.08.015
Finkel T, Deng CX, Mostoslavsky R (2009) Recent progress in the biology and physiology of sirtuins. Nature 460:587–591. https://doi.org/10.1038/nature08197
Ghavidel A, Baxi K, Prusinkiewicz M, Swan C, Belak ZR, Eskiw CH, Carvalho CE, Harkness TA (2018) Rapid nuclear exclusion of Hcm1 in aging Saccharomyces cerevisiae leads to vacuolar alkalization and replicative senescence. G3 (bethesda, Md.) 8:1579–1592. https://doi.org/10.1534/g3.118.200161
Gietz RD, Akio S (1988) New yeast-Escherichia coli shuttle vectors constructed with in vitro mutagenized yeast genes lacking six-base pair restriction sites. Gene 74:527–534. https://doi.org/10.1016/0378-1119(88)90185-0
Hadwan MH (2018) Simple spectrophotometric assay for measuring catalase activity in biological tissues. BMC Biochem 19:1–8. https://doi.org/10.1186/s12858-018-0097-5
Hartig A, Ruis H (1986) Nucleotide sequence of the Saccharomyces cerevisiae CTT1 gene and deduced amino-acid sequence of yeast catalase T. Eur J Biochem 160:487–490. https://doi.org/10.1111/j.1432-1033.1986.tb10065.x
He C, Zhou C, Kennedy BK (2018) The yeast replicative aging model. Biochim Biophys Acta (BBA) Mol Basis Dis 1864:2690–2696. https://doi.org/10.1016/j.bbadis.2018.02.023
Hendrickson DG, Soifer I, Wranik BJ, Kim G, Robles M, Gibney PA, McIsaac RS (2018) A new experimental platform facilitates assessment of the transcriptional and chromatin landscapes of aging yeast. Elife 7:e39911. https://doi.org/10.7554/eLife.39911
Hughes AL, Gottschling DE (2012) An early age increase in vacuolar pH limits mitochondrial function and lifespan in yeast. Nature 492:261–265. https://doi.org/10.1038/nature11654
James J, Fiji N, Roy D, Andrew DMG, Shihabudeen MS, Chattopadhyay D, Thirumurugan K (2015) A rapid method to assess reactive oxygen species in yeast using H2DCF-DA. Anal Methods 7:8572–8575. https://doi.org/10.1039/C5AY02278A
Janke C, Magiera MM, Rathfelder N, Taxis C, Reber S, Maekawa H, Moreno-Borchart A, Doenges G, Schwob E, Schiebel E, Knop M (2004) A versatile toolbox for PCR-based tagging of yeast genes: new fluorescent proteins, more markers and promoter substitution cassettes. Yeast 21:947–962. https://doi.org/10.1002/yea.1142
Janssens GE, Meinema AC, Gonzalez J, Wolters JC, Schmidt A, Guryev V, Bischoff R, Wit EC, Veenhoff LM, Heinemann M (2015) Protein biogenesis machinery is a driver of replicative aging in yeast. Elife 4:e08527. https://doi.org/10.7554/eLife.08527
Jin X, Cao X, Liu B (2021) Isolation of aged yeast cells using biotin-streptavidin affinity purification. In: Yeast protocols. Springer
Kaeberlein M (2010) Lessons on longevity from budding yeast. Nature 464:513–519. https://doi.org/10.1038/nature08981
Kaeberlein M, Kirkland KT, Fields S, Kennedy BK (2004) Sir2-independent life span extension by calorie restriction in yeast. PLoS Biol 2:e296. https://doi.org/10.1371/journal.pbio.0020296
Knorre DA, Azbarova AV, Galkina KV, Feniouk BA, Severin FF (2018) Replicative aging as a source of cell heterogeneity in budding yeast. Mech Ageing Dev 176:24–31. https://doi.org/10.1016/j.mad.2018.09.001
Kumar S, de Boer R, van der Klei IJ (2018) Yeast cells contain a heterogeneous population of peroxisomes that segregate asymmetrically during cell division. J Cell Sci 131:jcs207522. https://doi.org/10.1242/jcs.207522
Kuravi K, Nagotu S, Krikken AM, Sjollema K, Deckers M, Erdmann R, Veenhuis M, Van Der Klei IJ (2006) Dynamin-related proteins Vps1p and Dnm1p control peroxisome abundance in Saccharomyces cerevisiae. J Cell Sci 119:3994–4001. https://doi.org/10.1242/jcs.03166
Lam YT, Aung-Htut MT, Lim YL, Yang H, Dawes IW (2011) Changes in reactive oxygen species begin early during replicative aging of Saccharomyces cerevisiae cells. Free Radic Biol Med 50:963–970. https://doi.org/10.1016/j.freeradbiomed.2011.01.013
Laun P, Pichova A, Madeo F, Fuchs J, Ellinger A, Kohlwein S, Dawes I, Fröhlich KU, Breitenbach M (2001) Aged mother cells of Saccharomyces cerevisiae show markers of oxidative stress and apoptosis. Mol Microbiol 39:1166–1173. https://doi.org/10.1111/j.1365-2958.2001.02317.x
Lefevre SD, van Roermund CW, Wanders RJ, Veenhuis M, Van der Klei IJ (2013) The significance of peroxisome function in chronological aging of Saccharomyces cerevisiae. Aging Cell 12:784–793. https://doi.org/10.1111/acel.12113
Legakis JE, Koepke JI, Jedeszko C, Barlaskar F, Terlecky LJ, Edwards HJ, Walton PA, Terlecky SR (2002) Peroxisome senescence in human fibroblasts. Mol Biol Cell 13:4243–4255. https://doi.org/10.1091/mbc.e02-06-0322
Lindstrom DL, Gottschling DE (2009) The mother enrichment program: a genetic system for facile replicative life span analysis in Saccharomyces cerevisiae. Genetics 183:413–422. https://doi.org/10.1534/genetics.109.106229
Longo VD, Shadel GS, Kaeberlein M, Kennedy B (2012) Replicative and chronological aging in Saccharomyces cerevisiae. Cell Metab 16:18–31. https://doi.org/10.1016/j.cmet.2012.06.002
Lushchak VI, Gospodaryov DV (2005) Catalases protect cellular proteins from oxidative modification in Saccharomyces cerevisiae. Cell Biol Int 29:187–192. https://doi.org/10.1016/j.cellbi.2004.11.001
Mao X, Bharti P, Thaivalappil A, Cao K (2020) Peroxisomal abnormalities and catalase deficiency in Hutchinson-Gilford Progeria Syndrome. Aging (albany NY) 12:5195–5208. https://doi.org/10.18632/aging.102941
Matos L, Gouveia AM, Almeida H (2015) ER stress response in human cellular models of senescence. J Gerontol A Biol Sci Med Sci 70:924–935. https://doi.org/10.1093/gerona/glu129
Mesquita A, Weinberger M, Silva A, Sampaio-Marques B, Almeida B, Leão C, Costa V, Rodrigues F, Burhans WC, Ludovico P (2010) Caloric restriction or catalase inactivation extends yeast chronological lifespan by inducing H2O2 and superoxide dismutase activity. Proc Natl Acad Sci USA 107:15123–15128. https://doi.org/10.1073/pnas.1004432107
Mortimer RK, Johnston JR (1959) Life span of individual yeast cells. Nature 183:1751–1752. https://doi.org/10.1038/1831751a0
Müller I, Zimmermann M, Becker D, Flömer M (1980) Calendar life span versus budding lifespan of Saccharomyces cerevisiae. Mech Ageing Dev 12:47–52. https://doi.org/10.1016/0047-6374(80)90028-7
Niccoli T, Partridge L (2012) Ageing as a risk factor for disease. Curr Biol 22:R741–R752. https://doi.org/10.1016/j.cub.2012.07.024
Ocampo A, Barrientos A (2011) Quick and reliable assessment of chronological life span in yeast cell populations by flow cytometry. Mech Ageing Dev 132:315–323. https://doi.org/10.1016/j.mad.2011.06.007
Okumoto K, El Shermely M, Natsui M, Kosako H, Natsuyama R, Marutani T, Fujiki Y (2020) The peroxisome counteracts oxidative stresses by suppressing catalase import via Pex14 phosphorylation. Elife 9:e55896. https://doi.org/10.7554/eLife.55896
Payne BA, Chinnery PF (2015) Mitochondrial dysfunction in aging: much progress but many unresolved questions. Biochim Biophys Acta (BBA) Bioenerg 1847:1347–1353. https://doi.org/10.1016/j.bbabio.2015.05.022
Perić M, Dib PB, Dennerlein S, Musa M, Rudan M, Lovrić A, Nikolić A, Šarić A, Sobočanec S, Mačak Ž (2016) Crosstalk between cellular compartments protects against proteotoxicity and extends lifespan. Sci Rep 6:1–12. https://doi.org/10.1038/srep28751
Pernice WM, Vevea JD, Pon LA (2016) A role for Mfb1p in region-specific anchorage of high-functioning mitochondria and lifespan in Saccharomyces cerevisiae. Nat Commun 7:10595. https://doi.org/10.1038/ncomms10595
Powell CD, Quain DE, Smart KA (2003) Chitin scar breaks in aged Saccharomyces cerevisiae. Microbiology 149:3129–3137. https://doi.org/10.1099/mic.0.25940-0
Pozniakovsky AI, Knorre DA, Markova OV, Hyman AA, Skulachev VP, Severin FF (2005) Role of mitochondria in the pheromone- and amiodarone-induced programmed death of yeast. J Cell Biol 168:257–269. https://doi.org/10.1083/jcb.200408145
Rottensteiner H, Stein K, Sonnenhol E, Erdmann R (2003) Conserved function of pex11p and the novel pex25p and pex27p in peroxisome biogenesis. Mol Biol Cell 14:4316–4328. https://doi.org/10.1091/mbc.e03-03-0153
Ruetenik A, Barrientos A (2015) Dietary restriction, mitochondrial function and aging: from yeast to humans. Biochim Biophys Acta 1847:1434–1447. https://doi.org/10.1016/j.bbabio.2015.05.005
Scheckhuber CQ (2020) Characterization of survival and stress resistance in S. cerevisiae mutants affected in peroxisome inheritance and proliferation, Δ inp1 and Δ pex11. Folia Microbiol 65:423–429. https://doi.org/10.1007/s12223-019-00724-0
Scheckhuber C, Erjavec N, Tinazli A, Hamann A, Nyström T, Osiewacz H (2007) Reducing mitochondrial fission results in increased life span and fitness of two fungal ageing models. Nat Cell Biol 9:99–105. https://doi.org/10.1038/ncb1524
Scheckhuber CQ, Wanger RA, Mignat CA, Osiewacz HD (2011) Unopposed mitochondrial fission leads to severe lifespan shortening. Cell Cycle 10:3105–3110. https://doi.org/10.4161/cc.10.18.17196
Seo AY, Joseph A-M, Dutta D, Hwang JC, Aris JP, Leeuwenburgh C (2010) New insights into the role of mitochondria in aging: mitochondrial dynamics and more. J Cell Sci 123:2533–2542. https://doi.org/10.1242/jcs.070490
Sinclair DA, Guarente L (1997) Extrachromosomal rDNA circles—a cause of aging in yeast. Cell 91:1033–1042. https://doi.org/10.1016/s0092-8674(00)80493-6
Smeal T, Claus J, Kennedy B, Cole F, Guarente L (1996) Loss of transcriptional silencing causes sterility in old mother cells of S. cerevisiae. Cell 84:633–642. https://doi.org/10.1016/S0092-8674(00)81038-7
Sorokin MI, Knorre DA, Severin FF (2014) Early manifestations of replicative aging in the yeast Saccharomyces cerevisiae. Microb Cell 1:37–42. https://doi.org/10.15698/mic2014.01.122
Steinkraus K, Kaeberlein M, Kennedy BK (2008) Replicative aging in yeast: the means to the end. Annu Rev Cell Dev Biol 24:29–54. https://doi.org/10.1146/annurev.cellbio.23.090506.123509
Stępień K, Wojdyła D, Nowak K, Mołoń M (2020) Impact of curcumin on replicative and chronological aging in the Saccharomyces cerevisiae yeast. Biogerontology 21:109–123. https://doi.org/10.1007/s10522-019-09846-x
Tam YYC, Torres-Guzman JC, Vizeacoumar FJ, Smith JJ, Marelli M, Aitchison JD, Rachubinski RA (2003) Pex11-related proteins in peroxisome dynamics: a role for the novel peroxin Pex27p in controlling peroxisome size and number in Saccharomyces cerevisiae. Mol Biol Cell 14:4089–4102. https://doi.org/10.1091/mbc.e03-03-0150
Ušaj MM, Brložnik M, Kaferle P, Žitnik M, Wolinski H, Leitner F, Kohlwein SD, Zupan B, Petrovič U (2015) Genome-wide localization study of yeast Pex11 identifies peroxisome-mitochondria interactions through the ERMES complex. J Mol Biol 427:2072–2087. https://doi.org/10.1016/j.jmb.2015.03.004
Van Zandycke S, Sohier P, Smart K (2002) The impact of catalase expression on the replicative lifespan of Saccharomyces cerevisiae. Mech Ageing Dev 123:365–373. https://doi.org/10.1016/s0047-6374(01)00382-7
Wang IH, Chen HY, Wang YH, Chang KW, Chen YC, Chang CR (2014) Resveratrol modulates mitochondria dynamics in replicative senescent yeast cells. PLoS ONE 9:e104345. https://doi.org/10.1371/journal.pone.0104345
Woldringh C, Fluiter K, Huls P (1995) Production of senescent cells of Saccharomyces cerevisiae by centrifugal elutriation. Yeast 11:361–369. https://doi.org/10.1002/yea.320110409
Xie Z, Zhang Y, Zou K, Brandman O, Luo C, Ouyang Q, Li H (2012) Molecular phenotyping of aging in single yeast cells using a novel microfluidic device. Aging Cell 11:599–606. https://doi.org/10.1111/j.1474-9726.2012.00821.x
Zhang Y, Wong HS (2021) Are mitochondria the main contributor of reactive oxygen species in cells? J Exp Biol 224:jeb221606. https://doi.org/10.1242/jeb.221606
Zubko EI, Zubko MK (2014) Deficiencies in mitochondrial DNA compromise the survival of yeast cells at critically high temperatures. Microbiol Res 169:185–195. https://doi.org/10.1016/j.micres.2013.06.011
Funding
This work was supported by the Department of Biotechnology (DBT), Government of India [BT/PR16325/NER/95/117/2015], [BT/PR25097/NER/95/1013/2017] and Top-up of start-up Grant from IIT Guwahati.
Author information
Authors and Affiliations
Contributions
RD performed the experiments, prepared figures and tables and wrote the draft of the manuscript. SG performed experiments. SN wrote and critically edited the manuscript, and edited and conceived the concept for the manuscript. All authors read and approved the final manuscript.
Corresponding author
Ethics declarations
Conflict of interest
The authors declare that they have no conflicts of interest.
Ethical statement
This article does not contain any studies with human participants or animals performed by any of the authors.
Additional information
Communicated by Michael Polymenis.
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Supplementary Information
Below is the link to the electronic supplementary material.
Rights and permissions
About this article
Cite this article
Deb, R., Ghose, S. & Nagotu, S. Increased peroxisome proliferation is associated with early yeast replicative ageing. Curr Genet 68, 207–225 (2022). https://doi.org/10.1007/s00294-022-01233-3
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00294-022-01233-3