Maternal transmission of mitochondrial diseases

• Published in: Genetics and molecular biology Vol. 43; no. 1 suppl. 1; p. e20190095
• Main Authors: Chiaratti, Marcos R, Macabelli, Carolina H, Augusto Neto, José Djaci, Grejo, Mateus Priolo, Pandey, Anand Kumar, Perecin, Felipe, Collado, Maite Del
• Format: Journal Article
• Language: English
• Published: Brazil Sociedade Brasileira de Genética 01.01.2020
• Subjects: BIOCHEMISTRY & MOLECULAR BIOLOGY; GENETICS & HEREDITY; germline; metabolism; mitochondrial dynamics; mtDNA; Oocyte; metabolism; germline; mtDNA; Oocyte; mitochondrial dynamics
• ISSN: 1415-4757; 1678-4685; 1678-4685
• DOI: 10.1590/1678-4685-GMB-2019-0095

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.