What Are the Roles of Mitochondrial Stress Responses and Mitohormesis in Neurodegenerative Disorders?

Mitochondrial dysfunction is a key pathogenic component of neurodegenerative disorders. Mitochondrial stress, created by accumulation of misfolded proteins, reactive oxygen species, and other mechanisms, triggers signals that promote changes in protein translation and gene transcription aimed at protecting and restoring mitochondrial function and maintaining cellular homeostasis. These quality control responses are the integrated stress response and the mitochondrial unfolded protein response. When triggered by mild mitochondrial stress, these adaptive responses promote mitohormesis, which enhances cell survival and lifespan. The exchange of information between mitochondria allows mitochondrial stress in specific tissues to initiate beneficial adaptations affecting mitochondrial populations in remote tissues and organs. Experimental and human observational studies indicate that approaches to trigger mitohormesis, such as physical exercise, have beneficial effects in neurodegenerative disorders.