Mechanisms of mitochondria and autophagy crosstalk

Abstract

Autophagy is a cellular survival pathway that recycles intracellular components to compensate for nutrient depletion and ensures the appropriate degradation of organelles. Mitochondrial number and health are regulated by mitophagy, a process by which excessive or damaged mitochondria are subjected to autophagic degradation. Autophagy is thus a key determinant for mitochondrial health and proper cell function. Mitophagic malfunction has been recently proposed to contribute to progressive neuronal loss in Parkinson's disease. In addition to autophagy's significance in mitochondrial integrity, several lines of evidence suggest that mitochondria can also substantially influence the autophagic process. The mitochondria's ability to influence and be influenced by autophagy places both elements (mitochondria and autophagy) in a unique position where defects in one or the other system could increase the risk to various metabolic and autophagic related diseases.

Acknowledgments

We would like to thank Brenda Kostelecky and Tim Lammermann for critically reading the manuscript. We apologize for those studies we could not include in this review due to space constrains. A.S.R. was supported through a postdoctoral fellowship of the German Research Foundation (DFG).

Figures and Tables

Figure 1 Model for mitochondria-autophagy crosstalk. In this model, we depict the main intersection between in autophagy-mitochondrial crosstalk from the side of (1) autophagy and (2) mitochondria. (1) Autophagy shapes mitochondrial health and number through the selective degradation of mitochondria in a process termed mitophagy. Elimination of damaged mitochondria is facilitated by mitochondrial fission and promotes cell survival. Mitophagic malfunction leads to the accumulation of dysfunctional mitochondria and makes the cell more susceptible to MMP and apoptosis. When cell death is induced, apoptotic executers inactivate pro-autophagic proteins, thus inhibiting autophagy. (2) Autophagic degradation of mitochondria is affected by mitochondrial shape/function, with heavily fused mitochondria being a poor substrate that evades autophagic degradation. Mitochondria, furthermore, are able to control autophagic induction and autophagsomal biogenesis from mitochondria (or other autohagosomal origins such as the er) through mitochondrial localized proteins and/or metabolic products (such as ROS and ATP).