Mitochondria, autophagy and age-associated neurodegenerative diseases: New insights into a complex interplay

Highlights

• Mitochondria, the energy generating organelles in eukaryotes, play essential roles in diverse cellular processes.

• Mitochondrial dysfunction contributes to ageing and disease.

• Mitophagy, a specific form of autophagy, targets damaged mitochondria for degradation.

• Mitophagy defects have been implicated in senescent decline and susceptibility to neurodegeneration.

Abstract

Mitochondria represent the major bioenergetic hub coordinating cellular and organismal homeostasis. The underlying causes of many pathologies tormenting humans converge on impaired mitochondrial maintenance. Mitochondria-specific autophagy (mitophagy), a cellular catabolic process targeting mitochondria, holds a prominent role in mitochondrial quality control. In addition to core autophagic machinery components, mitophagy exploits a variety of molecules that identify damaged or superfluous mitochondria and mediate their elimination. Signaling pathways integrating environmental and genetic stimuli interact with key mitophagy effectors to activate cellular stress response mechanisms, ultimately modulating health and lifespan. Here, we review the signaling cascades and molecular mechanisms that govern the process of mitophagy and discuss their involvement in ageing and neurodegeneration. This article is part of a Special Issue entitled: Mitochondrial Dysfunction in Aging.