ArticleThe Journal of biological chemistry2016
p46Shc Inhibits Thiolase and Lipid Oxidation in Mitochondria.
Article in The Journal of biological chemistry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 21 citations in OpenAlex.
- P46Shc Inhibits Mitochondrial ACAA2 Thiolase, Exacerbating Mitochondrial Injury and Inflammation in Aging Livers.The American journal of pathology · 2025Article
- Distribution of the p66Shc Adaptor Protein Among Mitochondrial and Mitochondria-Associated Membranes Fractions in Normal and Oxidative Stress Conditions.International journal of molecular sciences · 2024Article
- The ketone body β-hydroxybutyrate shifts microglial metabolism and suppresses amyloid-β oligomer-induced inflammation in human microglia.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2023Article
- ACAA2 is a novel molecular indicator for cancers with neuroendocrine phenotype.British journal of cancer · 2023Article
- Transcriptional and metabolic programs promote the expansion of follicular helper T cells in lupus-prone mice.iScience · 2023Article
- Bistability in fatty-acid oxidation resulting from substrate inhibition.PLoS computational biology · 2021Article
- Double p52Shc/p46Shc Rat Knockout Demonstrates Severe Gait Abnormalities Accompanied by Dilated Cardiomyopathy.International journal of molecular sciences · 2021Article
- Nonphagocytic Activation of NOX2 Is Implicated in Progressive Nonalcoholic Steatohepatitis During Aging.Hepatology (Baltimore, Md.) · 2020Article
- Transcriptome analysis suggests a compensatory role of the cofactors coenzyme A and NADScientific reports · 2019Article
- The p52 isoform of SHC1 is a key driver of breast cancer initiation.Breast cancer research : BCR · 2019Article
- Computational identification and validation of alternative splicing in ZSF1 rat RNA-seq data, a preclinical model for type 2 diabetic nephropathy.Scientific reports · 2018Article
- The promiscuous enzyme medium-chain 3-keto-acyl-CoA thiolase triggers a vicious cycle in fatty-acid beta-oxidation.PLoS computational biology · 2017Article
- Mice with low levels of Shc proteins display reduced glycolytic and increased gluconeogenic activities in liver.Biochemistry and biophysics reports · 2016Article
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 2 countries.
Funding
Abstract
Although the p46Shc isoform has been known to be mitochondrially localized for 11 years, its function in mitochondria has been a mystery. We confirmed p46Shc to be mitochondrially localized and showed that the major mitochondrial partner of p46Shc is the lipid oxidation enzyme 3-ketoacylCoA thiolase ACAA2, to which p46Shc binds directly and with a strong affinity. Increasing p46Shc expression inhibits, and decreasing p46Shc stimulates enzymatic activity of thiolase in vitro Thus, we suggest p46Shc to be a negative mitochondrial thiolase activity regulator, and reduction of p46Shc expression activates thiolase. This is the first demonstration of a protein that directly binds and controls thiolase activity. Thiolase was thought previously only to be regulated by metabolite balance and steady-state flux control. Thiolase is the last enzyme of the mitochondrial fatty acid beta-oxidation spiral, and thus is important for energy metabolism. Mice with reduction of p46Shc are lean, resist obesity, have higher lipid oxidation capacity, and increased thiolase activity. The thiolase-p46Shc connection shown here in vitro and in organello may be an important underlying mechanism explaining the metabolic phenotype of Shc-depleted mice in vivo.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.