ArticleThe EMBO journal2023
Mitochondrial morphology controls fatty acid utilization by changing CPT1 sensitivity to malonyl-CoA.
Article in The EMBO journal, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 109 papers, 1 of them a synthesis that pooled it.
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Who cites it
109 citing papers in PubMed, 1 synthesis or guideline pooled it, 159 citations in OpenAlex.
- Food-derived dihydromyricetin and metabolic dysfunction-associated steatotic liver disease: a preclinical systematic review and meta-analysis.Frontiers in nutrition · 2026Pooled it
- Nutrient and non-nutrient regulators of insulin secretion.Nature reviews. Endocrinology · 2026Review
- Fasting requires Peroxiredoxin 2 and Peroxiredoxin 6 to coordinate redox dependent mitochondrial and lipid remodelling in Caenorhabditis elegans.Redox biology · 2026Article
- Mitochondrial NCLX couples glucagon- and PDE2A-Dependent signals to regulate hepatic lipid metabolism.Molecular metabolism · 2026Article
- Article
- Mechanisms and therapeutic potential of AMPK signaling pathway in the regulation of lipid metabolism.Molecular biology reports · 2026Review
- Transglutaminase 2 Deletion Enhances Astrocyte-to-Neuron Metabolic Support and Attenuates Subacute Pathology Following Repetitive Mild Traumatic Brain Injury.bioRxiv : the preprint server for biology · 2026Article
- Rewiring Lipid Metabolism: PINK1 as a Central Regulator of Mitochondrial Homeostasis in Parkinson's Disease.International journal of molecular sciences · 2026Review
- Crosstalk collapse: mitochondria-centric organelle network disruption in ovarian aging.Cell communication and signaling : CCS · 2026Review
- Compositional recalibrations of cardiolipin integrate loss of stearoyl-CoA desaturase 1 activity with mitochondrial decay in lipid-laden pancreatic β-cells.Cell communication and signaling : CCS · 2026Article
- Review
- STREMI: a dual-function upstream ORF-encoded regulator of mitochondrial cristae architecture.EMBO reports · 2026Article
- RAB5A regulates cell proliferation and lipid metabolism by modulating mitochondrial ROS via AMPK signaling pathway in ovarian granulosa cells.Redox biology · 2026Article
- Mitochondrial homeostasis: the central hub governing the progression of atherosclerosis.Precision clinical medicine · 2026Review
- Alternative organelle targeting of OPA1 mediates fatty acid release from lipid droplets.bioRxiv : the preprint server for biology · 2026Article
- Growth differentiation factor 15 mitigates lipotoxic steatosis by preserving mitochondrial morphodynamics and augmenting fatty acid oxidation in hepatocytes and liver organoids.Diabetes, obesity & metabolism · 2026Article
- Mechanisms of fatty acid metabolism in tumor metastasis and targeted therapeutic strategies.Discover oncology · 2026Review
- Immune regulators PALS-25 and PALS-22 localize to mitochondria and regulate mitochondrial fragmentation iniScience · 2026Article
- The expanding role of mitochondria-lipid droplet contacts in liver and their disruption by MASLD.Nature metabolism · 2026Article
- FKBP51 disrupts the insulin signaling pathway and impairs mitochondrial bioenergetics in HepG2 cells.Scientific reports · 2026Article
49 more citing papers are in PubMed but not listed here.
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Authors and funding
21 authors at 6 institutions in 4 countries.
Funding
Abstract
Changes in mitochondrial morphology are associated with nutrient utilization, but the precise causalities and the underlying mechanisms remain unknown. Here, using cellular models representing a wide variety of mitochondrial shapes, we show a strong linear correlation between mitochondrial fragmentation and increased fatty acid oxidation (FAO) rates. Forced mitochondrial elongation following MFN2 over-expression or DRP1 depletion diminishes FAO, while forced fragmentation upon knockdown or knockout of MFN2 augments FAO as evident from respirometry and metabolic tracing. Remarkably, the genetic induction of fragmentation phenocopies distinct cell type-specific biological functions of enhanced FAO. These include stimulation of gluconeogenesis in hepatocytes, induction of insulin secretion in islet β-cells exposed to fatty acids, and survival of FAO-dependent lymphoma subtypes. We find that fragmentation increases long-chain but not short-chain FAO, identifying carnitine O-palmitoyltransferase 1 (CPT1) as the downstream effector of mitochondrial morphology in regulation of FAO. Mechanistically, we determined that fragmentation reduces malonyl-CoA inhibition of CPT1, while elongation increases CPT1 sensitivity to malonyl-CoA inhibition. Overall, these findings underscore a physiologic role for fragmentation as a mechanism whereby cellular fuel preference and FAO capacity are determined.
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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.