Mitochondrial DNA replication and repair defects: Clinical phenotypes and therapeutic interventions

Roy, Abhipsa, Kandettu, Amoolya, Ray, Swagat and Chakrabarty, Sanjiban (2022) Mitochondrial DNA replication and repair defects: Clinical phenotypes and therapeutic interventions. Biochimica et Biophysica Acta (BBA) - Bioenergetics . ISSN 0005-2728

Full content URL: https://doi.org/10.1016/j.bbabio.2022.148554

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Mitochondrial DNA replication and repair defects: Clinical phenotypes and therapeutic interventions
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Abstract

Mitochondria is a unique cellular organelle involved in multiple cellular processes and is critical for maintaining cellular homeostasis. This semi-autonomous organelle contains its circular genome – mtDNA (mitochondrial DNA), that undergoes continuous cycles of replication and repair to maintain the mitochondrial genome integrity. The majority of the mitochondrial genes, including mitochondrial replisome and repair genes, are nuclear-encoded. Although the repair machinery of mitochondria is quite efficient, the mitochondrial genome is highly susceptible to oxidative damage and other types of exogenous and endogenous agent-induced DNA damage, due to the absence of protective histones and their proximity to the main ROS production sites. Mutations in replication and repair genes of mitochondria can result in mtDNA depletion and deletions subsequently leading to mitochondrial genome instability. The combined action of mutations and deletions can result in compromised mitochondrial genome maintenance and lead to various mitochondrial disorders. Here, we review the mechanism of mitochondrial DNA replication and repair process, key proteins involved, and their altered function in mitochondrial disorders. The focus of this review will be on the key genes of mitochondrial DNA replication and repair machinery and the clinical phenotypes associated with mutations in these genes.

Keywords:mtDNA replication, POLG, Base-excision repair, LIG3, CPEO
Subjects:C Biological Sciences > C440 Molecular Genetics
C Biological Sciences > C130 Cell Biology
C Biological Sciences > C741 Medical Biochemistry
C Biological Sciences > C700 Molecular Biology, Biophysics and Biochemistry
C Biological Sciences > C100 Biology
Divisions:College of Science > School of Life Sciences
ID Code:48716
Deposited On:28 Mar 2022 13:53

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