Mitophagy in neurological disorders

Journal of Neuroinflammation

Deyuan Li¹  Lijun Zhang¹  Lei Dai² 

[1] Department of Pediatrics, West China Second University Hospital, Sichuan University, 610041, Chengdu, China;Key Laboratory of Birth Defects and Related Disease of Women and Children (Sichuan University), Ministry of Education, 610041, Chengdu, Sichuan, China;State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center for Biotherapy, 610041, Chengdu, Sichuan, China;

关键词: Mitophagy;    Autophagy;    Neurological diseases;    Alzheimer's disease;    Huntington's disease;    Stroke;   

DOI  :  10.1186/s12974-021-02334-5

来源: Springer

【 摘 要 】

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.

【 授权许可】

CC BY