Disturb mitochondrial associated proteostasis: Neurodegeneration and imperfect ageing

Frontiers in Cell and Developmental Biology

Cell and Developmental Biology

Sumit Kinger¹  Prashant Kumar¹  Amit Mishra¹  Akash Choudhary¹  Yuvraj Anandrao Jagtap¹  Ankur Rakesh Dubey¹  Ravi Kumar Gutti²  Krishna Mohan Poluri³  Sarika Singh⁴  Hem Chandra Jha⁵ 

[1] Cellular and Molecular Neurobiology Unit, Indian Institute of Technology Jodhpur, Jodhpur, Rajasthan, India;Department of Biochemistry, School of Life Sciences, University of Hyderabad, Hyderabad, India;Department of Biotechnology, Indian Institute of Technology Roorkee, Centre for Nanotechnology, Indian Institute of Technology Roorkee, Roorkee, Uttarakhand, India;Division of Neuroscience and Ageing Biology, Division of Toxicology and Experimental Medicine, CSIR-Central Drug Research Institute, Lucknow, India;Infection Bioengineering Group, Department of Biosciences and Biomedical Engineering, Indian Institute of Technology Indore, Indore, Simrol, India;

关键词: neurodegeneration;    mitostasis;    autophagy;    proteasome;    oxidative stress;    mitochondria;   

DOI  :  10.3389/fcell.2023.1146564

 received in 2023-01-17, accepted in 2023-02-27,  发布年份 2023

来源: Frontiers

【 摘 要 】

The disturbance in mitochondrial functions and homeostasis are the major features of neuron degenerative conditions, like Parkinson’s disease, Amyotrophic Lateral Sclerosis, and Alzheimer’s disease, along with protein misfolding. The aberrantly folded proteins are known to link with impaired mitochondrial pathways, further contributing to disease pathogenesis. Despite their central significance, the implications of mitochondrial homeostasis disruption on other organelles and cellular processes remain insufficiently explored. Here, we have reviewed the dysfunction in mitochondrial physiology, under neuron degenerating conditions. The disease misfolded proteins impact quality control mechanisms of mitochondria, such as fission, fusion, mitophagy, and proteasomal clearance, to the detriment of neuron. The adversely affected mitochondrial functional roles, like oxidative phosphorylation, calcium homeostasis, and biomolecule synthesis as well as its axes and contacts with endoplasmic reticulum and lysosomes are also discussed. Mitochondria sense and respond to multiple cytotoxic stress to make cell adapt and survive, though chronic dysfunction leads to cell death. Mitochondria and their proteins can be candidates for biomarkers and therapeutic targets. Investigation of internetworking between mitochondria and neurodegeneration proteins can enhance our holistic understanding of such conditions and help in designing more targeted therapies.

【 授权许可】

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Copyright © 2023 Jagtap, Kumar, Kinger, Dubey, Choudhary, Gutti, Singh, Jha, Poluri and Mishra.