ACSF3
- Known as:
- ACSF3
- Catalog number:
- 001044A
- Product Quantity:
- 250ul
- Category:
- -
- Supplier:
- ABM
- Gene target:
- ACSF3
Related genes to: ACSF3
- Gene:
- ACSF3 NIH gene
- Name:
- acyl-CoA synthetase family member 3
- Previous symbol:
- -
- Synonyms:
- -
- Chromosome:
- 16q24.3
- Locus Type:
- gene with protein product
- Date approved:
- 2007-10-17
- Date modifiied:
- 2018-05-03
Related products to: ACSF3
Related articles to: ACSF3
- Hepatic daily rhythms are coordinated by feeding and the molecular circadian clock, ensuring metabolic homeostasis. Disrupted feeding schedules promote circadian misalignment and metabolic diseases but the underlying mechanisms remain scarce. Post-translational modifications have emerged as key regulators of circadian metabolic outputs. Here, we show that the mitochondrial enzyme Acyl-CoA synthetase family member 3 (ACSF3) oscillates in phase with different feeding schedules to drive rhythmic lysine-malonylation and coordinate daily hepatic metabolism. Hepatic Acsf3 knockdown drastically affected lysine-malonylation rhythms, decreased fasting glycemia, insulin sensitivity, and AKT phosphorylation, indicative of perturbed glucose homeostasis. Concomitantly, Acsf3 knockdown shifted lipid oxidation from mitochondria to peroxisomes, enhanced lipogenesis and triglyceride synthesis, while increasing diurnal autophagy. Multi-omics profiling uncovered specific lysine-malonylation targets in glycolysis, the tricarboxylic acid (TCA) cycle, fatty-acid oxidation and autophagy. Our findings uncover hepatic ACSF3 as a pivotal molecular nexus that integrates feeding time with dynamic protein lysine-malonylation and orchestrates the diurnal rhythm of liver metabolism. - Source: PubMed
Publication date: 2026/08/07
Le Questel EnoraBesnard CharlèneAtger FlorianFoucher YolèneTollec AlwénaPakulska VictoriaOliveira Arsênio RodriguesCloteau ChloéGourdel MathildeNemazanyy IvanThouzeau AmélieLe May CédricCroyal MikaëlCouté YohannJacobi DavidCariou BertrandMauvoisin Daniel - Malonate is often described as an endogenous inhibitor of complex II of the electron transport chain. However, the cellular source of malonate is unclear, and current knowledge concerning its metabolism is limited to the action of a single enzyme, Acyl-CoA Synthetase Family Member 3 (ACSF3), which converts malonate to malonyl-CoA in the mitochondrial matrix. One potential route of malonate metabolism downstream of ACSF3 is its consumption by the mitochondrial fatty acid synthesis (mtFAS) pathway. However, studies examining the link between ACSF3 and mtFAS have yielded conflicting results. We developed a novel mass spectrometry approach to perform stable isotope tracing into products of mtFAS, and found that while malonate is in fact a carbon source for mtFAS, ACSF3 is not required for malonate incorporation into mtFAS products. Using this method to trace other nutrients into mtFAS, we also found evidence of acetyl-CoA carboxylase 1 (ACC1)-dependent malonate synthesis from glucose. We further show that ACC1 is required for optimal mtFAS activity, with downstream effects on oxidative phosphorylation. Together these findings establish the malonate as a regulated endogenous intermediate that supports mtFAS activity and mitochondrial oxidative function. - Source: PubMed
Publication date: 2026/05/29
Wedan Riley JNorden Pieter RCanfield Morgan TEllis Abigail ESaxena SanskritiLongenecker Jacob ZDykstra MichelleSheldon Ryan DNowinski Sara M - To investigate the clinical characteristics, genetic variants and outcomes of children with combined malonic and methylmalonic aciduria (CMAMMA) caused by ACSF3 gene variant. This was a retrospective case series. Clinical manifestations, biochemical findings, genetic sequencing and outcomes were collected from 7 infants with CMAMMA who were evaluated at the Department of Pediatric Endocrinology and Genetic Metabolism, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine between December 2021 and November 2025. Blood acylcarnitine profiles were analyzed by tandem mass spectrometry, urinary organic acids by gas chromatography-mass spectrometry and causative variants by Sanger or next generation sequencing. The cohort included 6 males and 1 female, with an age at onset of 1.0 (0.4, 8.0) years and 6 patients did not experienced acute metabolic decompensation during the neonatal or infantile period. Five patients had varying degrees of developmental delay, including 1 patient with seizures and 1 patient with hypotonia. Biochemical analysis revealed elevated urinary methylmalonic acid level in all patients, and 5 patients also had elevated urinary malonic acid levels. Plasma propionylcarnitine (C3) and homocysteine levels were within normal ranges in all patients, while a mildly increased C3/acetylcarnitine (C2) ratio was observed in 1 patient. Five patients were unresponsive to vitamin B therapy. Genetic analysis identified 11 ACSF3 gene variants, including 2 novel variants, c.785C>T (p.A262V) and c.889T>A (p.Y297N). Follow-up assessments showed 5 patients exhibited severe or borderline developmental delay, 1 patient developed normally and 1 patient died. CMAMMA caused by ACSF3 variants is characterized by marked phenotypic heterogeneity and a subset of patients experience unfavorable outcomes. The predominant biochemical finding is elevated urinary methylmalonic acid, with or without concurrent elevation of malonic acid, while blood acylcarnitine profiles were often within the normal range. - Source: PubMed
Ding YDeng Y XHao L LZhi H JChen TZhan XHan L S - Acyl-conezyme A (CoA) synthetase family member 3 ( ACSF3 ) related combined malonic and methylmalonic aciduria (CMAMMA) is an inborn error of metabolism involving defective activation of malonic and methylmalonic acids to CoA derivatives. The resulting deficiency of malonyl-CoA disrupts mitochondrial fatty acid synthesis, lipid metabolism, and protein malonylation. Although regarded as a benign condition, studies have demonstrated that ACSF3 deficiency may lead to variable manifestations. - Source: PubMed
Publication date: 2026/05/27
Gokalp SabireBasan HacerOlgac AsburceKucukcongar Yavas AynurKilic Mustafa - We here propose a mitochondria-centered reinterpretation of the ACSF3 regulatory variant reported by Zhang et al., integrating advances in mitochondrial fatty acid synthesis and ACSF3-deficient models to link subcellular control of oxidative efficiency with organismal traits such as basal metabolic rate, height, and systemic growth regulation in humans. - Source: PubMed
Tucci Sara