Mitochondrial DNA: Distribution, Mutations, and Elimination.

Yan Yan,Song Song,Zeng Zeng,Liu Liu,Duanmu Duanmu

doi:10.3390/cells8040379

Abstract

Mitochondrion harbors its own DNA (mtDNA), which encodes many critical proteins for the assembly and activity of mitochondrial respiratory complexes. mtDNA is packed by many proteins to form a nucleoid that uniformly distributes within the mitochondrial matrix, which is essential for mitochondrial functions. Defects or mutations of mtDNA result in a range of diseases. Damaged mtDNA could be eliminated by mitophagy, and all paternal mtDNA are degraded by endonuclease G or mitophagy during fertilization. In this review, we describe the role and mechanism of mtDNA distribution and elimination. In particular, we focus on the regulation of paternal mtDNA elimination in the process of fertilization.

Highlights

Mitochondrion is a double-membrane organelle that generates about 90% of cell energy in the form of adenosine triphosphate (ATP) by the oxidative phosphorylation (OXPHOS) process in mammalian cells
Unlike the other organelles in a mammalian cell, mitochondria have a small amount of their own DNA, which is known as mitochondrial DNA, which encodes a series of crucial proteins for mitochondrial respiration
Among the identified nucleoid proteins, TFAM is the main protein of the nucleoid, and acts as a transcription factor of mitochondrial DNA (mtDNA) in mitochondria and plays an important role in nucleoid distribution and organization [7,8]. mtDNA distributes throughout the mitochondrial network, which is essential for the maintenance of mitochondrial functions

Summary

Introduction

Mitochondrion is a double-membrane organelle that generates about 90% of cell energy in the form of adenosine triphosphate (ATP) by the oxidative phosphorylation (OXPHOS) process in mammalian cells. The deficiency of mitochondrial fission caused by the loss of Drp leads to hyperfused mitochondria and enlarged mtDNA nucleoids characterized by mtDNA accumulation [54,61,62]. Additional, cholesterol is rich at the site of the ER-associated mitochondrial membrane (MAM), which is involved in mtDNA distribution and segregation [20,83,84]. ATAD3 (ATPase family AAA domain-containing protein 3), locating at the mitochondrial inner membrane, is colocalized with mitochondrial nucleoids in mammalian cells by binding to the D-loop of mtDNA (Figure 1B) [85,86]. The BAK-BAX play a major role in the mitochondria-mediated apoptotic pathway [90]; BAK/BAX form oligomers in the mitochondrial outer membrane and alter the permeability of the outer membrane, which result in the release of apoptotic factor cytochrome c [91,92]. Recent studies have found that paternal mitochondria containing mtDNA were selectively eliminated, either before or after fertilization, to prevent paternal mtDNA from transmiting to the generation [98]

Endonuclease G-Mediated Degradation of Paternal mtDNA

Mitophagy-Mediated Degradation of Paternal mtDNA

Findings

The Clearance of Mutant mtDNA