Signaling Pathways from Mitochondria to the Cytoplasm and Nucleus

Publisher Summary This chapter focuses on signals originating from mitochondria that are primarily small molecules with targets in the cytosol and the nucleus. It begins with a discussion of some general themes in the current literature. Following this, it presents few examples of specific signaling pathways, where the understanding has advanced significantly in recent years. The small molecules (ATP/ADP/AMP, NAD+/NADH, GSH/GSSG) that are continuously turned over in the cytosol and in the mitochondrial matrix are now recognized to be not only cofactors driving endergonic reactions, or donors/acceptors of electrons in redox reactions. In combination with Ca +2 , NO, cAMP, and cGMP they serve as allosteric effectors and in feedback mechanisms to control metabolic flux through numerous pathways, and they can also act as powerful elements in the modulation of gene expression. Major players involved in signaling pathways leading to transcriptional regulation have been identified: AMPK, PGC-1, PPARγ, and the sirtuins. Finally, the study states that it must be recognized that metabolism is not a subject to be ignored as history, but metabolism and bioenergetics are indispensable aspects of the expression of genetic information, development and differentiation, and ultimately the phenomenon of senescence and death. A challenge of the future is to measure accurate concentrations of each of these components in the various cellular compartments, to observe absolute and relative changes, and to incorporate all of these reactions into a computer model.