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

Autor(es)

Chiaratti, Marcos Roberto ^{[1, 2]} ; Garcia, Bruna Martins ^[1] ; Carvalho, Karen Freire ^[1] ; Machado, Thiago Simoes ^{[1, 2]} ; da Silva Ribeiro, Fernanda Karina ^[1] ; Macabelli, Carolina Habermann ^[1]

Afiliação do(s) autor(es)

^[1] Univ Fed Sao Carlos, Dept Genet & Evolucao, BR-13565905 Sao Carlos, SP - Brazil

^[2] Univ Sao Paulo, Fac Med Vet & Zootecnia, BR-05508270 Sao Paulo, SP - Brazil

• Tipo de documento: Artigo de Revisão
• Fonte: Cell Biology International; v. 42, n. 6, SI, p. 711-724, JUN 2018.
• Citações Web of Science: 6

Resumo

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)

• Processo FAPESP: 12/50231-6 - Bases moleculares da herança mitocondrial: o papel da fusão mitocondrial
• Beneficiário: Marcos Roberto Chiaratti
• Modalidade de apoio: Auxílio à Pesquisa - Jovens Pesquisadores
• Processo FAPESP: 16/11935-9 - Efeito do nocaute da mitofusina 2 sobre a mitocôndria, o retículo endoplasmático e a mitofagia em oócitos murinos
• Beneficiário: Bruna Martins Garcia
• Modalidade de apoio: Bolsas no Brasil - Mestrado
• Processo FAPESP: 17/05899-2 - Efeito do nocaute das mitofusinas no oócito murino: implicações para a fertilidade e herança mitocondrial
• Beneficiário: Marcos Roberto Chiaratti
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 16/11942-5 - Efeito do nocaute da mitofusina 1 sobre a fertilidade de oócitos murinos
• Beneficiário: Karen Freire Carvalho
• Modalidade de apoio: Bolsas no Brasil - Mestrado
• Processo FAPESP: 16/07868-4 - Efeito do nocaute das mitofusinas em fibroblastos embrionários murinos sobre a herança de DNA mitocondrial deletério
• Beneficiário: Carolina Habermann Macabelli
• Modalidade de apoio: Bolsas no Brasil - Doutorado