ArticleAutophagy2023
Selective autophagic degradation of ACLY (ATP citrate lyase) maintains citrate homeostasis and promotes oocyte maturation.
Article in Autophagy, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 55 citations in OpenAlex.
- Orchestrating Ovarian Dysfunction- The Role of Programmed Cell Death in PCOS.Cell biochemistry and biophysics · 2026Article
- Restoring glucose metabolic homeostasis to attenuate ovarian aging: mechanisms and clinical prospects.Journal of ovarian research · 2026Review
- Crosstalk collapse: mitochondria-centric organelle network disruption in ovarian aging.Cell communication and signaling : CCS · 2026Review
- The ATP-Citrate Lyase Subunit ACLA, Coordinates Rice Pollen Development by Coupling Transcriptional Regulation with Metabolic Homeostasis.Rice (New York, N.Y.) · 2026Article
- SPATA22 heterozygous variants drive premature ovarian insufficiency: mechanism of granulosa cells dysfunction and therapeutic potential of N-acetylcysteine (NAC) treatment.Reproductive biology and endocrinology : RB&E · 2026Article
- Effect of Vitrification on Lipidomics in Porcine Cumulus-Oocyte Complexes After In Vitro Maturation.Cells · 2026Article
- Combined Analysis of the Transcriptome and Metabolome at Different Tissue Glycogen Levels in Yili Horses.Animals : an open access journal from MDPI · 2026Article
- Critical roles of m6A demethylase FTO in ovarian aging.Biogerontology · 2026Review
- Article
- Autophagy dictates PHGDH-mediated serine metabolism in a timely manner to support oocyte development.Autophagy · 2026Article
- Mechanistic study on the role of multi-pathway autophagy in ovarian aging: literature review.Apoptosis : an international journal on programmed cell death · 2025Review
- Fosl2 facilitates chromatin accessibility to determine developmental events during follicular maturation.Nature communications · 2025Article
- Dietary Citrate Restores Age-Related Endothelial Cell Mitochondrial Dysfunction and Alleviates Atherosclerosis.Aging cell · 2025Article
- The cutting-edge progress of novel biomedicines in ovulatory dysfunction therapy.Acta pharmaceutica Sinica. B · 2025Review
- Autophagy in ovary: protective roles, pathological consequences, and unresolved issues.Journal of ovarian research · 2025Review
- Interplay of Oxidative Stress, Autophagy, and Rubicon in Ovarian Follicle Dynamics: Orchestrating Ovarian Aging.Antioxidants (Basel, Switzerland) · 2025Review
- Non-coding RNA-mediated granulosa cell dysfunction during ovarian aging: From mechanisms to potential interventions.Non-coding RNA research · 2025Review
- Chloroquine inhibits artificial oocyte activation induced by ethanol or SrThe Journal of reproduction and development · 2025Article
- The N6-methyladenosine landscape of ovarian development and aging highlights the regulation by RNA stability and chromatin state.Aging cell · 2025Article
- S100P is a ferroptosis suppressor to facilitate hepatocellular carcinoma development by rewiring lipid metabolism.Nature communications · 2025Article
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Authors and funding
21 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Macroautophagy/autophagy is a cellular and energy homeostatic mechanism that contributes to maintain the number of primordial follicles, germ cell survival, and anti-ovarian aging. However, it remains unknown whether autophagy in granulosa cells affects oocyte maturation. Here, we show a clear tendency of reduced autophagy level in human granulosa cells from women of advanced maternal age, implying a potential negative correlation between autophagy levels and oocyte quality. We therefore established a co-culture system and show that either pharmacological inhibition or genetic ablation of autophagy in granulosa cells negatively affect oocyte quality and fertilization ability. Moreover, our metabolomics analysis indicates that the adverse impact of autophagy impairment on oocyte quality is mediated by downregulated citrate levels, while exogenous supplementation of citrate can significantly restore the oocyte maturation. Mechanistically, we found that ACLY (ATP citrate lyase), which is a crucial enzyme catalyzing the cleavage of citrate, was preferentially associated with K63-linked ubiquitin chains and recognized by the autophagy receptor protein SQSTM1/p62 for selective autophagic degradation. In human follicles, the autophagy level in granulosa cells was downregulated with maternal aging, accompanied by decreased citrate in the follicular fluid, implying a potential correlation between citrate metabolism and oocyte quality. We also show that elevated citrate levels in porcine follicular fluid promote oocyte maturation. Collectively, our data reveal that autophagy in granulosa cells is a beneficial mechanism to maintain a certain degree of citrate by selectively targeting ACLY during oocyte maturation.
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