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Uncovering the important role of mitochondrial dynamics in oogenesis: impact on fertility and metabolic disorder transmission

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Abstract

Oocyte health is tightly tied to mitochondria given their role in energy production, metabolite supply, calcium (Ca2+) buffering, and cell death regulation, among others. In turn, mitochondrial function strongly relies on these organelle dynamics once cyclic events of fusion and fission (division) are required for mitochondrial turnover, positioning, content homogenization, metabolic flexibility, interaction with subcellular compartments, etc. Importantly, during oogenesis, mitochondria change their architecture from an “orthodox” elongated shape characterized by the presence of numerous transversely oriented cristae to a round-to-oval morphology containing arched and concentrically arranged cristae. This, along with evidence showing that mitochondrial function is kept quiescent during most part of oocyte development, suggests an important role of mitochondrial dynamics in oogenesis. To investigate this, recent works have downregulated/upregulated in oocytes the expression of key effectors of mitochondrial dynamics, including mitofusins 1 (MFN1) and 2 (MFN2) and the dynamin-related protein 1 (DRP1). As a result, both MFN1 and DRP1 were found to be essential to oogenesis and fertility, while MFN2 deletion led to offspring with increased weight gain and glucose intolerance. Curiously, neither MFN1/MFN2 deficiency nor DRP1 overexpression enhanced mitochondrial fragmentation, indicating that mitochondrial size is strictly regulated in oocytes. Therefore, the present work seeks to discuss the role of mitochondria in supporting oogenesis as well as recent findings connecting defective mitochondrial dynamics in oocytes with infertility and transmission of metabolic disorders.

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Marcos R. Chiaratti is funded by the São Paulo Research Foundation (FAPESP/Brazil – grants # 2017/04372-0 and 2020/15412-6), Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq/Brazil), the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES/Brazil – finance code 001), and the Academy of Medical Sciences-Newton Advanced Fellowship.

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Chiaratti, M.R. Uncovering the important role of mitochondrial dynamics in oogenesis: impact on fertility and metabolic disorder transmission. Biophys Rev 13, 967–981 (2021). https://doi.org/10.1007/s12551-021-00891-w

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