The mitochondrial stress responses: the Dr. Jekyll and Mr. Hyde of neuronal disorders

Neuronal disorders are associated with a profound loss of mitochondrial functions caused by various stress conditions, such as oxidative and metabolic stress, protein folding or import defects, and mitochondrial DNA alteration. Cells engage in different coordinated responses to safeguard mitochondrial homeostasis. In this review, we will explore the contribution of mitochondrial stress responses that are activated by the organelle to perceive these dangerous conditions, keep them under control and rescue the physiological condition of nervous cells. In the sections to come, particular attention will be dedicated to analyzing how compensatory mitochondrial hyperfusion, mitophagy, mitochondrial unfolding protein response, and apoptosis impact human neuronal diseases. Finally, we will discuss the relevance of the new concept: the mito-inflammation, a mitochondria-mediated inflammatory response that is recently found to cover a relevant role in the pathogenesis of diverse inflammatory-related diseases, including neuronal disorders.

Automated summary

Neuronal disorders are closely associated with the loss of mitochondrial functions, and mitochondria activate stress responses to perceive and control dangerous conditions while rescuing the physiological state of nerve cells. This review primarily discusses the impact of compensatory mitochondrial hyperfusion, mitophagy, mitochondrial unfolding protein response, and apoptosis on neurological diseases, as well as the relevance of mitochondria-mediated inflammatory response in the pathogenesis of these diseases.