The role of mitochondria in the female germline: Implications to fertility and inheritance of mitochondrial diseases

Author(s)

Chiaratti, Marcos Roberto ; Garcia, Bruna Martins ; Carvalho, Karen Freire ; Machado, Thiago Simoes ; da Silva Ribeiro, Fernanda Karina ; Macabelli, Carolina Habermann

• Document type: Journal article
• Source: Cell Biology International; v. 42, n. 6, p. 14-pg., 2018-06-01.

Abstract

Mitochondria play a fundamental role during development of the female germline. They are fragmented, round, and small. Despite these characteristics suggesting that they are inactive, there is accumulating evidence that mitochondrial dysfunctions are a major cause of infertility and generation of aneuploidies in humans. In addition, mitochondria and their own genomes (mitochondrial DNAmtDNA) may become damaged with time, which might be one reason why aging leads to infertility. As a result, mitochondria have been proposed as an important target for evaluating oocyte and embryo quality, and developing treatments for female infertility. On the other hand, mutations in mtDNA may cause mitochondrial dysfunctions, leading to severe diseases that affect 1 in 4,300 people. Moreover, very low levels of mutated mtDNA seem to be present in every person worldwide. These may increase with time and associate with late-onset degenerative diseases such as Parkinson disease, Alzheimer disease, and common cancers. Mutations in mtDNA are transmitted down the maternal lineage, following a poorly understood pattern of inheritance. Recent findings have indicated existence in the female germline of a purifying filter against deleterious mtDNA variants. Although the underlying mechanism of this filter is largely unknown, it has been suggested to rely on autophagic degradation of dysfunctional mitochondria or selective replication/transmission of non-deleterious variants. Thus, understanding the mechanisms regulating mitochondrial inheritance is important both to improve diagnosis and develop therapeutic tools for preventing transmission of mtDNA-encoded diseases. (AU)

• FAPESP's process: 17/05899-2 - Effect of the knockout of mitofusins on mouse oocyte: implications to fertility and mitochondrial inheritance
• Grantee: Marcos Roberto Chiaratti
• Support Opportunities: Regular Research Grants
• FAPESP's process: 16/11935-9 - Effect of the knockout of mitofusin 2 on mitochondria, endoplasmic reticulum and mitophagy in murine oocytes
• Grantee: Bruna Martins Garcia
• Support Opportunities: Scholarships in Brazil - Master
• FAPESP's process: 16/07868-4 - Effect of the mitofusins knockout on the inheritance of deleterious mitochondrial DNA in mouse embryonic fibroblasts
• Grantee: Carolina Habermann Macabelli
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 16/11942-5 - Fertility effect of the knockout of Mitofusin 1 on murine oocytes
• Grantee: Karen Freire Carvalho
• Support Opportunities: Scholarships in Brazil - Master
• FAPESP's process: 12/50231-6 - Molecular basis of mitochondrial inheritance: the role of mitochondrial fusion
• Grantee: Marcos Roberto Chiaratti
• Support Opportunities: Research Grants - Young Investigators Grants