Positioning mitochondrial plasticity within cellular signaling cascades

Mitochondria evolved from alpha-proteobacteria captured within a host between two and three billion years ago. This origin resulted in the formation of a double-layered organelle resulting in four distinct sub-compartments: the outer membrane, the intermembrane space, the inner membrane and the matrix. The inner membrane is organized in cristae, harboring the respiratory chain and ATP synthase complexes responsible of the oxidative phosphorylation, the main energy-generating system of the cell. It is generally considered that the ultrastructure of the inner membrane provides a large variety of morphologies that facilitate metabolic output. This classical view of mitochondria as bean-shaped organelles was static until in the last decade when new imaging studies and genetic screens provided a more accurate description of a dynamic mitochondrial reticulum that fuse and divide continuously. Since then significant findings have been made in the study of machineries responsible for fusion, fission and motility, however the mechanisms and signals that regulate mitochondrial dynamics are only beginning to emerge. A growing body of evidence indicates that metabolic and cellular signals influence mitochondrial dynamics, leading to a new understanding of how changes in mitochondrial shape can have a profound impact on the functional output of the organelle. The mechanisms that regulate mitochondrial morphology are incompletely understood, but evidence to date suggests that the morphology machinery is modulated through the use of post-translational modifications, including nucleotide-binding proteins, phosphorylation, ubiquitination, SUMOylation, and changes in the lipid environment. This review focuses on the molecular switches that control mitochondrial dynamics and the integration of mitochondrial morphology within cellular signaling cascades. (C) 2008 Elsevier B.V. All rights reserved.