Neuronal Mitophagy: Friend or Foe?

Abstract

Maintenance of neuronal homeostasis is a challenging task, due to unique cellular organization and bioenergetic demands of post-mitotic neurons. It is increasingly appreciated that impairment of mitochondrial homeostasis represents an early sign of neuronal dysfunction that is common in both age-related neurodegenerative as well as in neurodevelopmental disorders. Mitochondrial selective autophagy, known as mitophagy, regulates mitochondrial number ensuring cellular adaptation in response to several intracellular and environmental stimuli. Mounting evidence underlines that deregulation of mitophagy levels has an instructive role in the process of neurodegeneration. Although mitophagy induction mediates the elimination of damaged mitochondria and confers neuroprotection, uncontrolled runaway mitophagy could reduce mitochondrial content overstressing the remaining organelles and eventually triggering neuronal cell death. Unveiling the molecular mechanisms of neuronal mitophagy and its intricate role in neuronal survival and cell death, will assist in the development of novel mitophagy modulators to promote cellular and organismal homeostasis in health and disease.

Effects of Iron and Zinc on Mitochondria: Potential Mechanisms of Glaucomatous Injury

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Publication Trends on Mitophagy in the World and China: A 16-Year Bibliometric Analysis

“…Mitophagy is a form of autophagy that mediates the removal of defective or redundant mitochondria ( Doxaki and Palikaras 2020 ; Wang et al, 2021 ). And it is the only known way to selectively remove entire mitochondria ( D'Acunzo et al, 2019 ).…”

Mitochondria-affecting small molecules ameliorate proteostasis defects associated with neurodegenerative diseases

“…Stimulation of mitophagy has proven to be a promising therapeutic target for neurodegenerative diseases 69 and may be beneficial for healthy aging. Using a high-throughput, high-content phenotypic screen, we obtained and characterized eight compounds that lead to increased accumulation of PINK-1/PINK1.…”

“…The accumulation of mitochondrial damage, and concomitant degradation of function, is associated with both aging and neurodegenerative disease. Mitophagy also appears to be inherently limited in mature neurons (reviewed in 69 ), which may explain why this tissue is more sensitive to mitochondrial damage in the first place. Increasingly, it has been hypothesized and demonstrated that increasing mitophagy in these cells may promote better cellular health and aging (reviewed in 69 ).…”