ArticleNature communications2023
SAPS3 subunit of protein phosphatase 6 is an AMPK inhibitor and controls metabolic homeostasis upon dietary challenge in male mice.
Article in Nature communications, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 13 citations in OpenAlex.
- AURKA-mediated destabilization of SAPS3 drives ferroptosis evasion via 7-dehydrocholesterol biosynthesis in colorectal cancer.Cell death & disease · 2026Article
- AMPK at the interface of nutrient sensing, metabolic flux and energy homeostasis.Nature metabolism · 2026Review
- The inhibitory SAPS3-AMPK interaction detected in HEK293 cells is not detectable in muscle or liver from humans or mice.FEBS letters · 2025Article
- The protein phosphatase 6 subunit SAPS3 modulates lifespan by regulating metabolism.Science advances · 2025Article
- Article
- PPP6R3-mediated dephosphorylation regulates mRNA translation during spermatogonial differentiation.Communications biology · 2025Article
- Coptisine inhibits lipid accumulation in high glucose- and palmitic acid-induced HK-2 cells by regulating the AMPK/ACC/CPT-1 signaling pathway.Naunyn-Schmiedeberg's archives of pharmacology · 2025Article
- Protein phosphatase 4 maintains the survival of primordial follicles by regulating autophagy in oocytes.Cell death & disease · 2024Article
- Protein phosphatase 6 promotes stemness of colorectal cancer cells.Cancer science · 2024Article
- Comparative Transcriptome Analysis of the Hepatopancreas fromAnimals : an open access journal from MDPI · 2024Article
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
Inhibition of AMPK is tightly associated with metabolic perturbations upon over nutrition, yet the molecular mechanisms underlying are not clear. Here, we demonstrate the serine/threonine-protein phosphatase 6 regulatory subunit 3, SAPS3, is a negative regulator of AMPK. SAPS3 is induced under high fat diet (HFD) and recruits the PP6 catalytic subunit to deactivate phosphorylated-AMPK, thereby inhibiting AMPK-controlled metabolic pathways. Either whole-body or liver-specific deletion of SAPS3 protects male mice against HFD-induced detrimental consequences and reverses HFD-induced metabolic and transcriptional alterations while loss of SAPS3 has no effects on mice under balanced diets. Furthermore, genetic inhibition of AMPK is sufficient to block the protective phenotype in SAPS3 knockout mice under HFD. Together, our results reveal that SAPS3 is a negative regulator of AMPK and suppression of SAPS3 functions as a guardian when metabolism is perturbed and represents a potential therapeutic strategy to treat metabolic syndromes.
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