Maternal transmission of mitochondrial diseases.

Marcos R Chiaratti,Anand Kumar Pandey,Maite Del Collado,José Djaci Augusto Neto,Felipe Perecin,Mateus Priolo Grejo,Carolina H Macabelli

doi:10.1590/1678-4685-gmb-2019-0095

Abstract

Given the major role of the mitochondrion in cellular homeostasis, dysfunctions of this organelle may lead to several common diseases in humans. Among these, maternal diseases linked to mitochondrial DNA (mtDNA) mutations are of special interest due to the unclear pattern of mitochondrial inheritance. Multiple copies of mtDNA are present in a cell, each encoding for 37 genes essential for mitochondrial function. In cases of mtDNA mutations, mitochondrial malfunctioning relies on mutation load, as mutant and wild-type molecules may co-exist within the cell. Since the mutation load associated with disease manifestation varies for different mutations and tissues, it is hard to predict the progeny phenotype based on mutation load in the progenitor. In addition, poorly understood mechanisms act in the female germline to prevent the accumulation of deleterious mtDNA in the following generations. In this review, we outline basic aspects of mitochondrial inheritance in mammals and how they may lead to maternally-inherited diseases. Furthermore, we discuss potential therapeutic strategies for these diseases, which may be used in the future to prevent their transmission.

Highlights

The mitochondrion gained its deserved reputation in cell biology due to its role as the cellular powerhouse, with most of the adenosine triphosphate (ATP) in eukaryotic cells being supplied by this organelle (Wallace, 2013)
Amongst mitochondria-associated diseases, those primarily linked to mitochondrial DNA mutations have been a topic of great interest given their severe outcome and unclear pattern of inheritance (Craven et al, 2017)
MtDNA mutations can associate with nuclear mutations, leading to common diseases in humans such as cancer, diabetes, Alzheimer, and Parkinson (Wallace 2011; Schon et al, 2012; Stewart and Chinnery 2015)

Summary

Introduction

The mitochondrion gained its deserved reputation in cell biology due to its role as the cellular powerhouse, with most of the adenosine triphosphate (ATP) in eukaryotic cells being supplied by this organelle (Wallace, 2013). Amongst mitochondria-associated diseases, those primarily linked to mitochondrial DNA (mtDNA) mutations have been a topic of great interest given their severe outcome and unclear pattern of inheritance (Craven et al, 2017). Thereby, recent findings have associated obesity with mitochondrial dysfunction in oocytes and increased risk of metabolic diseases in offspring (Wu et al, 2015; Saben et al, 2016).

Results

Conclusion