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 is a preview of subscription content, log in to check access.
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.
Ristow M, Schmeisser S (2011) Extending life span by increasing oxidative stress. Free Radic Biol Med 51:327–336CrossRefGoogle Scholar
Lòpez-Otìn C, Blasco MA, Partridge L et al (2013) The hallmarks of aging. Cell 153:1194–1217CrossRefGoogle Scholar
Jang JY, Blum A, Liu J et al (2018) The role of mitochondria in aging. JCI 128:3662–3670CrossRefGoogle Scholar
Chandel NS (2015) Evolution of mitochondria as signalling organelles. Cell Metab 22:204–206CrossRefGoogle Scholar
Di Benedetto G, Pendin D, Greotti E et al (2014) Ca2+ and cAMP cross-talk in mitochondria. J Physiol 592:305–312CrossRefGoogle Scholar
Di Benedetto G, Gerbino A, Lefkimmiatis K (2018) Shaping mitochondrial dynamics: the role of cAMP signalling. BBRC 500:65–74PubMedGoogle Scholar
Acin-Perez R, Salazar E, Kamenetsky M et al (2009) Cyclic AMP produced inside mitochondria regulates oxidative phosphorylation. Cell Metab 9:265–276CrossRefGoogle Scholar
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
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
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
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
Giorgio V, Guo L, Bassot C et al (2018) Calcium and the regulation of the mitochondrial permeability transition. Cell Calcium 70:56–63CrossRefGoogle Scholar
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
Kelly MP (2018) Cyclic nucleotide signaling changes associated with normal aging and age related diseases of the brain. Cell Signal 42:281–291CrossRefGoogle Scholar