Mitochondrial protein import dysfunction: mitochondrial disease, neurodegenerative disease and cancer

FEBS Letters

article

Catherine S. Palmer¹  Alexander J. Anderson¹  Diana Stojanovski¹ 

[1] Department of Biochemistry and Molecular Biology and The Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne

关键词: Alzheimer's disease;    cancer;    Huntington's disease;    mitochondria;    neurodegeneration;    Parkinson's disease;    protein import;    TIM;    TOM;   

DOI  :  10.1002/1873-3468.14022

来源: John Wiley & Sons Ltd.

【 摘 要 】

The majority of proteins localised to mitochondria are encoded by the nuclear genome, with approximately 1500 proteins imported into mammalian mitochondria. Dysfunction in this fundamental cellular process is linked to a variety of pathologies including neuropathies, cardiovascular disorders, myopathies, neurodegenerative diseases and cancer, demonstrating the importance of mitochondrial protein import machinery for cellular function. Correct import of proteins into mitochondria requires the co-ordinated activity of multimeric protein translocation and sorting machineries located in both the outer and inner mitochondrial membranes, directing the imported proteins to the destined mitochondrial compartment. This dynamic process maintains cellular homeostasis, and its dysregulation significantly affects cellular signalling pathways and metabolism. This review summarises current knowledge of the mammalian mitochondrial import machinery and the pathological consequences of mutation of its components. In addition, we will discuss the role of mitochondrial import in cancer, and our current understanding of the role of mitochondrial import in neurodegenerative diseases including Alzheimer's disease, Huntington's disease and Parkinson's disease.

【 授权许可】

Unknown