期刊
DNA AND CELL BIOLOGY
卷 38, 期 1, 页码 23-40出版社
MARY ANN LIEBERT, INC
DOI: 10.1089/dna.2018.4292
关键词
TOMM; TIMM; mitochondrial protein import; disease; genetics; gene and protein expression
资金
- National Research Foundation of South Africa [106052]
- South African Medical Research Council (Self-Initiated Research Grant)
- Stellenbosch University Faculty of Medicine and Health Science Postdoctoral Fellowship
- PROMOS scholarship by the mobility program of the Deutscher Akademischer Austauschienst (DAAD)
- International Office of the Humboldt-Universitat zu Berlin
Mitochondria are critical for cellular survival, and for their proper functioning, translocation of similar to 1500 proteins across the mitochondrial membranes is required. The translocase of the outer (TOMM) and inner mitochondrial membrane (TIMM) complexes are major components of this translocation machinery. Through specific processes, preproteins and other molecules are imported, translocated, and directed to specific mitochondrial compartments for their function. In this study, we review the association of subunits of these complexes with human disease. Pathogenic mutations have been identified in the TIMM8A (DDP) and DNAJC19 (TIMM14) genes and are linked to Mohr-Tranebj AE rg syndrome and dilated cardiomyopathy syndrome (with and without ataxia), respectively. Polymorphisms in TOMM40 have been associated with Alzheimer's disease, frontotemporal lobar degeneration, Parkinson's disease with dementia, dementia with Lewy bodies, nonpathological cognitive aging, and various cardiovascular-related traits. Furthermore, reduced protein expression levels of several complex subunits have been associated with Parkinson's disease, Meniere's disease, and cardiovascular disorders. However, increased mRNA and protein levels of complex subunits are found in cancers. This review highlights the importance of the mitochondrial import machinery in human disease and stresses the need for further studies. Ultimately, this knowledge may prove to be critical for the development of therapeutic modalities for these conditions.
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