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Review

The Journey of Mitochondrial Protein Import and the Roadmap to Follow

by
Mary Oluwadamilola Haastrup
1,2,
Kunwar Somesh Vikramdeo
1,2,
Seema Singh
1,2,3,
Ajay Pratap Singh
1,2,3 and
Santanu Dasgupta
1,2,3,*
1
Mitchell Cancer Institute, University of South Alabama, Mobile, AL 36604, USA
2
Department of Pathology, College of Medicine, University of South Alabama, Mobile, AL 36617, USA
3
Department of Biochemistry and Molecular Biology, University of South Alabama, Mobile, AL 36688, USA
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2023, 24(3), 2479; https://doi.org/10.3390/ijms24032479
Submission received: 28 December 2022 / Revised: 19 January 2023 / Accepted: 25 January 2023 / Published: 27 January 2023
(This article belongs to the Special Issue Mitochondria in Human Diseases)

Abstract

Mitochondria are double membrane-bound organelles that play critical functions in cells including metabolism, energy production, regulation of intrinsic apoptosis, and maintenance of calcium homeostasis. Mitochondria are fascinatingly equipped with their own genome and machinery for transcribing and translating 13 essential proteins of the oxidative phosphorylation system (OXPHOS). The rest of the proteins (99%) that function in mitochondria in the various pathways described above are nuclear-transcribed and synthesized as precursors in the cytosol. These proteins are imported into the mitochondria by the unique mitochondrial protein import system that consists of seven machineries. Proper functioning of the mitochondrial protein import system is crucial for optimal mitochondrial deliverables, as well as mitochondrial and cellular homeostasis. Impaired mitochondrial protein import leads to proteotoxic stress in both mitochondria and cytosol, inducing mitochondrial unfolded protein response (UPRmt). Altered UPRmt is associated with the development of various disease conditions including neurodegenerative and cardiovascular diseases, as well as cancer. This review sheds light on the molecular mechanisms underlying the import of nuclear-encoded mitochondrial proteins, the consequences of defective mitochondrial protein import, and the pathological conditions that arise due to altered UPRmt.
Keywords: mitochondria; mitochondrial protein import machineries; proteins; mitochondrial unfolded protein response; diseases mitochondria; mitochondrial protein import machineries; proteins; mitochondrial unfolded protein response; diseases
Graphical Abstract

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MDPI and ACS Style

Haastrup, M.O.; Vikramdeo, K.S.; Singh, S.; Singh, A.P.; Dasgupta, S. The Journey of Mitochondrial Protein Import and the Roadmap to Follow. Int. J. Mol. Sci. 2023, 24, 2479. https://doi.org/10.3390/ijms24032479

AMA Style

Haastrup MO, Vikramdeo KS, Singh S, Singh AP, Dasgupta S. The Journey of Mitochondrial Protein Import and the Roadmap to Follow. International Journal of Molecular Sciences. 2023; 24(3):2479. https://doi.org/10.3390/ijms24032479

Chicago/Turabian Style

Haastrup, Mary Oluwadamilola, Kunwar Somesh Vikramdeo, Seema Singh, Ajay Pratap Singh, and Santanu Dasgupta. 2023. "The Journey of Mitochondrial Protein Import and the Roadmap to Follow" International Journal of Molecular Sciences 24, no. 3: 2479. https://doi.org/10.3390/ijms24032479

APA Style

Haastrup, M. O., Vikramdeo, K. S., Singh, S., Singh, A. P., & Dasgupta, S. (2023). The Journey of Mitochondrial Protein Import and the Roadmap to Follow. International Journal of Molecular Sciences, 24(3), 2479. https://doi.org/10.3390/ijms24032479

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