Signaling pathways in mitochondrial dysfunction and aging.
Mitochondria are central players in the determination of cell life and death. They are essential for energy production, since most cellular ATP is produced in their matrix by the oxidative phosphorylation pathway. At the same time, mitochondria are the main regulators of apoptotic cell death, mediating both extrinsic (cell-surface receptor mediated) and intrinsic apoptotic pathways. Reactive oxygen species (ROS) accumulate as side products of the electron transport chain, causing mitochondrial damage. Non-functional mitochondria accumulate in aged individuals, and cell homeostasis is maintained by removing damaged mitochondria by an autophagic process called "mitophagy". In addition, mitochondrial ROS represent signaling molecules leading to autophagy, consisting in the bulk degradation of cytosolic portions. When cell homeostasis is perturbed, and cytosolic components are damaged, autophagy represents a defense mechanism aimed at removing non-functional proteins and organelles. If this is not sufficient, cell death occurs with distinct morphological hallmarks from apoptosis. This binary choice integrates a number of critical information converging on a number of common regulatory elements. In this review, the focus will be placed on the central role of mitochondria in the cross-talk between autophagy and apoptosis, highlighting the signaling pathways and molecular machinery impinging on these organelles.
Mammucari
Cristina
C
Department of Biomedical Sciences, University of Padova, Padova, Italy.
Rizzuto
Rosario
R
D000367:Age Factors; D000375:Aging / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D017209:Apoptosis; D001343:Autophagy; D002118:Calcium / Q000378:metabolism; D006801:Humans; D008928:Mitochondria / Q000378:metabolism* / Q000473:pathology; D028361:Mitochondrial Diseases / Q000378:metabolism* / Q000473:pathology; D018384:Oxidative Stress; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction
D017382:Reactive Oxygen Species; D002118:Calcium