Emerging mitochondrial signaling mechanisms in physiology, aging processes, and as drug targets

Advances in research on mitochondria have elucidated their importance in cell survival and cell death regulation in addition to their function in energy production. Mitochondria are further implicated in various metabolic and aging-related diseases, which are now assumed to be caused by misregulation of physiological systems rather than pure accumulation of oxidative damage. Thus, the signaling mechanisms within mitochondria and between the organelle and its environment have gained interest as potential drug targets. Emerging mitochondrial signaling systems with potential for exploiting them for therapeutic intervention include, among others, the NAD+-dependent protein deacetylases of the Sirtuin family, the redox enzyme p66Shc, and enzymes of the cyclic adenosine monophosphate (cAMP) signaling pathways. Here, we discuss functions of these signaling systems in mitochondria, their roles in aging processes and disease, and their potential to serve as therapeutic targets.

Research Highlights
► Mitochondria are implicated in various metabolic and aging-related diseases.
► Signaling systems previously studied in other compartments act inside mitochondria.
► They include reversible acetylation, cyclic nucleotides, and redox signaling.
► The enzymes involved are attractive targets for drug development.