Mitophagy in neurological disorders

• Published in: Journal of neuroinflammation Vol. 18; no. 1; p. 297
• Main Authors: Zhang, Lijun, Dai, Lei, Li, Deyuan
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 22.12.2021; BioMed Central; BMC
• Subjects: Age; Alzheimer's disease; Amino acids; Amyotrophic lateral sclerosis; Animals; Autophagy; Autophagy (Cytology); Binding sites; Care and treatment; Chronic illnesses; Energy metabolism; Epilepsy; Fatty acids; Health aspects; Humans; Huntington's disease; Huntingtons disease; Hypoxia; Intracellular; Ischemia; Kinases; Microscopy; Mitochondria; Mitochondria - pathology; Mitophagy; Movement disorders; Mutation; Nervous system; Nervous system diseases; Nervous System Diseases - pathology; Neurodegeneration; Neurodegenerative Diseases; Neurological diseases; Neurological disorders; Neuroprotection; Organelles; Parkinson's disease; Phosphatase; Phosphorylation; Proteins; Quality control; Review; Stroke; Traumatic brain injury; China; Neurological diseases; Stroke; Huntington's disease; Mitophagy; Alzheimer's disease; Autophagy
• ISSN: 1742-2094; 1742-2094
• DOI: 10.1186/s12974-021-02334-5

Selective autophagy is an evolutionarily conserved mechanism that removes excess protein aggregates and damaged intracellular components. Most eukaryotic cells, including neurons, rely on proficient mitophagy responses to fine-tune the mitochondrial number and preserve energy metabolism. In some circumstances (such as the presence of pathogenic protein oligopolymers and protein mutations), dysfunctional mitophagy leads to nerve degeneration, with age-dependent intracellular accumulation of protein aggregates and dysfunctional organelles, leading to neurodegenerative disease. However, when pathogenic protein oligopolymers, protein mutations, stress, or injury are present, mitophagy prevents the accumulation of damaged mitochondria. Accordingly, mitophagy mediates neuroprotective effects in some forms of neurodegenerative disease (e.g., Alzheimer's disease, Parkinson's disease, Huntington's disease, and Amyotrophic lateral sclerosis) and acute brain damage (e.g., stroke, hypoxic-ischemic brain injury, epilepsy, and traumatic brain injury). The complex interplay between mitophagy and neurological disorders suggests that targeting mitophagy might be applicable for the treatment of neurodegenerative diseases and acute brain injury. However, due to the complexity of the mitophagy mechanism, mitophagy can be both harmful and beneficial, and future efforts should focus on maximizing its benefits. Here, we discuss the impact of mitophagy on neurological disorders, emphasizing the contrast between the positive and negative effects of mitophagy.