Mitochondrial signalling and homeostasis: from cell biology to neurological disease. Issue 2 (February 2023)

• Record Type: Journal Article
• Authors: Collier, Jack J.; Oláhová, Monika; McWilliams, Thomas G.; Taylor, Robert W.
• Is Part Of: Trends in neurosciences. Volume 46:Issue 2(2023)
• Page Start: 137
• Page End: 152
• Publication Date: 2023-02
• Subjects: mitochondrial-derived vesicles -- metabolism -- quality control -- mitochondria–lysosome axis -- inflammation -- immunity; Neurology -- Periodicals; Neurophysiology -- Periodicals; Neurobiology -- Periodicals; 612.8
• DOI: 10.1016/j.tins.2022.12.001
• Languages: English
• ISSNs: 0166-2236

Abstract

Highlights: Mitochondria, in addition to their well-described roles in energy metabolism, have emerged as dynamic signalling hubs that coordinate diverse cellular processes. These mitochondrial roles can be broadly categorized into ones involving contact sites, trafficking (shedding of mitochondrial-derived vesicles), and transmission (production and release of metabolites). Mitochondrial immunomodulation plays an important role in neurodegeneration, for instance, in Parkinson's disease and amyotrophic lateral sclerosis, and during neuroinvasive infection such as with Zika virus. Mitochondrial homeostasis is supported by compartmentalized processes that facilitate nanoscale proteostasis, as well as by the endolysosome system that can receive, digest and recycle mitochondrial subcompartments or entire organelles. These systems have also become integrated within mitochondrial signalling pathways to regulate metabolic plasticity. Physiological mitophagy in neural cells recycles mitochondria in response to metabolic signals and stressors. Mitochondrial recycling enables both damage control and metabolic plasticity, such as regulation of iron homeostasis. Abstract: Efforts to understand how mitochondrial dysfunction contributes to neurodegeneration have primarily focussed on the role of mitochondria in neuronal energy metabolism. However, progress in understanding the etiological nature of emerging mitochondrial functions has yielded new ideas about the mitochondrial basis of neurological disease. Studies aimed at deciphering how mitochondria signal through interorganellar contacts, vesicular trafficking, and metabolic transmission have revealed that mitochondrial regulation of immunometabolism, cell death, organelle dynamics, and neuroimmune interplay are critical determinants of neural health. Moreover, the homeostatic mechanisms that exist to protect mitochondrial health through turnover via nanoscale proteostasis and lysosomal degradation have become integrated within mitochondrial signalling pathways to support metabolic plasticity and stress responses in the nervous system. This review highlights how these distinct mitochondrial pathways converge to influence neurological health and contribute to disease pathology.