ArticleAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2024
AMPK Suppression Due to Obesity Drives Oocyte mtDNA Heteroplasmy via ATF5-POLG Axis.
Article in Advanced science (Weinheim, Baden-Wurttemberg, Germany), 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed, 10 citations in OpenAlex.
- When to test: defining the earliest reliable time for pregnancy detection and its prognostic value after frozen embryo transfer.AJOG global reports · 2026Article
- Maternal Exercise Rescues Embryonic Osteogenesis Impaired due to POLG Mutation Through a Potential Apelin-ATF4 Axis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Elevated maternal non-esterified fatty acid concentrations during late gestation are associated with altered skeletal muscle development and mitochondrial dynamics related-markers in calves.Journal of animal science and biotechnology · 2026Article
- Exercise attenuates polycystic ovary syndrome development via improved mitochondrial proteostasis.American journal of physiology. Endocrinology and metabolism · 2026Article
- Maternal undernutrition inhibits fetal rumen development: novel miRNA-736-mediated dual targeting of E2F2 and MYBL2 in sheep.Journal of animal science and biotechnology · 2026Article
- Obesity and recurrent spontaneous abortion: the crucial role of weight management in pregnancy.Reproductive biology and endocrinology : RB&E · 2025Review
- The dual burden of obesity: decoding metabolism and female reproductive endocrinology.Frontiers in physiology · 2025Review
- Nuclear transfer leads to aberrant cell cycle regulation and translation, as determined by gene expression, and selection of mitochondrial DNA in porcine blastocysts.NAR molecular medicine · 2024Article
- AMPK Suppression Due to Obesity Drives Oocyte mtDNA Heteroplasmy via ATF5-POLG Axis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
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Authors and funding
9 authors at 4 institutions in 2 countries.
Funding
Abstract
Due to the exclusive maternal transmission, oocyte mitochondrial dysfunction reduces fertility rates, affects embryonic development, and programs offspring to metabolic diseases. However, mitochondrial DNA (mtDNA) are vulnerable to mutations during oocyte maturation, leading to mitochondrial nucleotide variations (mtSNVs) within a single oocyte, referring to mtDNA heteroplasmy. Obesity (OB) accounts for more than 40% of women at the reproductive age in the USA, but little is known about impacts of OB on mtSNVs in mature oocytes. It is found that OB reduces mtDNA content and increases mtSNVs in mature oocytes, which impairs mitochondrial energetic functions and oocyte quality. In mature oocytes, OB suppresses AMPK activity, aligned with an increased binding affinity of the ATF5-POLG protein complex to mutated mtDNA D-loop and protein-coding regions. Similarly, AMPK knockout increases the binding affinity of ATF5-POLG proteins to mutated mtDNA, leading to the replication of heteroplasmic mtDNA and impairing oocyte quality. Consistently, AMPK activation blocks the detrimental impacts of OB by preventing ATF5-POLG protein recruitment, improving oocyte maturation and mitochondrial energetics. Overall, the data uncover key features of AMPK activation in suppressing mtSNVs, and improving mitochondrial biogenesis and oocyte maturation in obese females.
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Registered trials
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