Mitochondria sentencing about cellular life and death: a matter of oxidative stress

Abstract

Mitochondria are crucial, multifunctional organelles which actively regulate cellular homeostasis. Their complex and diverse role includes maintenance of the cellular energetic balance through hosting several catabolic pathways which result in the process of oxidative phosphorylation, as well as enabling various fundamental anabolic processes and controlling Ca2+ distribution. Moreover, mitochondria are the main cellular generator of reactive oxygen species, which act as second messengers and when over-produced provoke a state of oxidative stress, a condition implicated in many pathologies. Importantly, mitochondria are directly involved in triggering different and complexly interconnected programs promoting cell survival or death. The aim of this review is to summarize the current understanding regarding mitochondrial implication in the main cellular pathways controlling cell "fate" such as apoptosis, autophagy (mitophagy), mitoptosis and necrosis with particular emphasis on the role that reactive oxygen species and oxidative stress may play in these phenomena. The literature extensively covers the topic of reactive oxygen species and apoptosis, fewer articles however deal with mitophagy or mitochondrial dynamics and very few mention the implication oxidative stress and redox modifications have for mitoptosis or necrosis. This review offers a global picture of the complex role of mitochondria in the regulation of cell "fate", referring specifically to the interconnection and balance between different cellular pathways of death and survival. Current knowledge regarding the involvement of these processes in particular human pathologies, specifically with respect to the implication of reactive oxygen species and oxidative stress, is also discussed.