A matter of life, death and diseases: mitochondria from a proteomic perspective.

ABSTRACT

Mitochondria are highly ordered, integrated organelles that energize cellular activities and contribute to programmed death by initiating disciplined apoptotic cascades. This review seeks to clarify our understanding of mitochondrial structural-functional integrity beyond the resolved nuclear genome by unraveling the dynamic mitochondrial proteome and elucidating proteome/genome interplay. The roles of mechanochemical coupling between mitoskeleton and cytoskeleton and crosstalk with other organelles in orchestrating cellular outcomes are explained. The authors also review the modulation of mitochondrial-related oxidative stress on apoptosis and cancer development and the context is applied to interpret pathogenetic events in neurodegenerative disorders and cardiovascular diseases. The accumulated proteomics evidence is used to describe the integral role that mitochondria play and how they influence other intracellular organelles. Possible mitochondrial-targeted therapeutic interventions are also discussed.