Mitochondrial communication in the context of aging

  • Konstantinos Lefkimmiatis
  • Francesca Grisan
  • Liliana F. Iannucci
  • Nicoletta C. Surdo
  • Tullio PozzanEmail author
  • Giulietta Di BenedettoEmail author
Short Communication


Mitochondria constantly contribute to the cell homeostasis and this, during the lifespan of a cell, takes its toll. Indeed, the functional decline of mitochondria appears correlated to the aging of the cell. The initial idea was that excessive production of reactive oxygen species (ROS) by functionally compromised mitochondria was the causal link between the decline of the organelle functions and cellular aging. However, in recent years accumulating evidence suggests that the contribution of mitochondria to cellular aging goes beyond ROS production. In this short review, we discuss how intracellular signalling, specifically the cAMP-signalling cascade, is involved in the regulation of mitochondrial functions and potentially in the processes that link mitochondrial status to cellular aging.


cAMP Signalling Mitochondria Aging 



This work was supported by the National Research Council of Italy (CNR), Research Project “Aging: molecular and technological innovations for improving the health of the elderly population” (Prot. MIUR 2867 25.11.2011).

Compliance with ethical standard

Conflict of interest

On behalf of all authors, the corresponding authors state that there is no conflict of interest.

Statement of human and animal rights

In the original work by the authors all applicable international, national, and/or institutional guidelines for the care and use of animals were followed. This article does not contain any studies with human participants performed by any of the authors.

Informed consent

Not applicable.


  1. 1.
    Ristow M, Schmeisser S (2011) Extending life span by increasing oxidative stress. Free Radic Biol Med 51:327–336CrossRefGoogle Scholar
  2. 2.
    Lòpez-Otìn C, Blasco MA, Partridge L et al (2013) The hallmarks of aging. Cell 153:1194–1217CrossRefGoogle Scholar
  3. 3.
    Jang JY, Blum A, Liu J et al (2018) The role of mitochondria in aging. JCI 128:3662–3670CrossRefGoogle Scholar
  4. 4.
    Finkel T (2015) The metabolic regulation of aging. Nat Med 21:1416–1423CrossRefGoogle Scholar
  5. 5.
    Chandel NS (2015) Evolution of mitochondria as signalling organelles. Cell Metab 22:204–206CrossRefGoogle Scholar
  6. 6.
    Di Benedetto G, Pendin D, Greotti E et al (2014) Ca2+ and cAMP cross-talk in mitochondria. J Physiol 592:305–312CrossRefGoogle Scholar
  7. 7.
    Di Benedetto G, Gerbino A, Lefkimmiatis K (2018) Shaping mitochondrial dynamics: the role of cAMP signalling. BBRC 500:65–74PubMedGoogle Scholar
  8. 8.
    Acin-Perez R, Salazar E, Kamenetsky M et al (2009) Cyclic AMP produced inside mitochondria regulates oxidative phosphorylation. Cell Metab 9:265–276CrossRefGoogle Scholar
  9. 9.
    Di Benedetto G, Scalzotto E, Mongillo M et al (2013) Mitochondrial Ca2+ uptake induces cyclic AMP generation in the matrix and modulates organelle ATP levels. Cell Metab 17:965–975CrossRefGoogle Scholar
  10. 10.
    Lefkimmiatis K, Leronni D, Hofer AM (2013) The inner and outer compartments of mitochondria are sites of distinct cAMP/PKA signaling dynamics. J Cell Biol 202:453–462CrossRefGoogle Scholar
  11. 11.
    Jakobsen E, Lange SC, Bak LK (2019) Soluble adenylyl cyclase-mediated cAMP signaling and the putative role of PKA and EPAC in cerebral mitochondrial function. J. Neurosci. Res. 97:1018–1038CrossRefGoogle Scholar
  12. 12.
    Burdyga A, Surdo NC, Monterisi S et al (2018) Phosphatases control PKA-dependent functional microdomains at the outer mitochondrial membrane. PNAS USA 115:E6497–E6506CrossRefGoogle Scholar
  13. 13.
    Giorgio V, Guo L, Bassot C et al (2018) Calcium and the regulation of the mitochondrial permeability transition. Cell Calcium 70:56–63CrossRefGoogle Scholar
  14. 14.
    Ogawa F, Murphy LC, Malavasi EL et al (2016) NDE1 and GSK3b associate with TRAK1 and regulate axonal mitochondrial motility: identification of cyclic AMP as a novel modulator of axonal mitochondrial trafficking. ACS Chem Neurosci 7:553–564CrossRefGoogle Scholar
  15. 15.
    Kelly MP (2018) Cyclic nucleotide signaling changes associated with normal aging and age related diseases of the brain. Cell Signal 42:281–291CrossRefGoogle Scholar

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© Springer Nature Switzerland AG 2020

Authors and Affiliations

  1. 1.Department of Molecular MedicineUniversity of PaviaPaviaItaly
  2. 2.Veneto Institute of Molecular MedicineFoundation for Advanced Biomedical ResearchPadovaItaly
  3. 3.Neuroscience InstituteNational Research Council of Italy (CNR)PadovaItaly
  4. 4.Department of Biomedical SciencesUniversity of PadovaPadovaItaly
  5. 5.Department of BiologyUniversity of PadovaPadovaItaly

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