ArticleThe Journal of biological chemistry2011
Uncoupling protein 3 (UCP3) modulates the activity of Sarco/endoplasmic reticulum Ca2+-ATPase (SERCA) by decreasing mitochondrial ATP production.
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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Who cites it
40 citing papers in PubMed, 79 citations in OpenAlex.
- Mitochondrial dysfunction is a key link involved in the pathogenesis of sick sinus syndrome: a review.Frontiers in cardiovascular medicine · 2024Review
- TMBIM5 is the CaEMBO reports · 2022Article
- Mitochondria-Mediated Cardiovascular Benefits of Sodium-Glucose Co-Transporter 2 Inhibitors.International journal of molecular sciences · 2022Review
- The Role of Thyroid Hormones on Skeletal Muscle Thermogenesis.Metabolites · 2022Review
- Mitochondrial CaInternational journal of molecular sciences · 2022Review
- The Uncoupling Proteins: A Systematic Review on the Mechanism Used in the Prevention of Oxidative Stress.Antioxidants (Basel, Switzerland) · 2022Review
- Acute RyR1 CaNature communications · 2021Article
- IFI6 depletion inhibits esophageal squamous cell carcinoma progression through reactive oxygen species accumulation via mitochondrial dysfunction and endoplasmic reticulum stress.Journal of experimental & clinical cancer research : CR · 2020Article
- Dehydroepiandrosterone protects against hepatic glycolipid metabolic disorder and insulin resistance induced by high fat via activation of AMPK-PGC-1α-NRF-1 and IRS1-AKT-GLUT2 signaling pathways.International journal of obesity (2005) · 2020Article
- Sodium-glucose co-transporter 2 inhibition as a mitochondrial therapy for atrial fibrillation in patients with diabetes?Cardiovascular diabetology · 2020Article
- Mitochondrial Uncoupling Proteins: Subtle Regulators of Cellular Redox Signaling.Antioxidants & redox signaling · 2018Review
- Rosuvastatin relieves myocardial ischemia/reperfusion injury by upregulating PPAR‑γ and UCP2.Molecular medicine reports · 2018Article
- Mitochondrial Dysfunction-Associated Arrhythmogenic Substrates in Diabetes Mellitus.Frontiers in physiology · 2018Review
- Optogenetic control of mitochondrial metabolism and CaProceedings of the National Academy of Sciences of the United States of America · 2017Article
- The antidepressant fluoxetine induces necrosis by energy depletion and mitochondrial calcium overload.Oncotarget · 2017Article
- PRMT1-mediated methylation of MICU1 determines the UCP2/3 dependency of mitochondrial Ca(2+) uptake in immortalized cells.Nature communications · 2016Article
- TMX1 determines cancer cell metabolism as a thiol-based modulator of ER-mitochondria Ca2+ flux.The Journal of cell biology · 2016Article
- UCP3 Regulates Single-Channel Activity of the Cardiac mCa1.The Journal of membrane biology · 2016Article
- The mitochondrial Ca2+ uniporter: regulation by auxiliary subunits and signal transduction pathways.American journal of physiology. Cell physiology · 2016Review
- Restoration of Mitochondrial Cardiolipin Attenuates Cardiac Damage in Swine Renovascular Hypertension.Journal of the American Heart Association · 2016Article
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The uncoupling proteins UCP2 and UCP3 have been postulated to catalyze Ca(2+) entry across the inner membrane of mitochondria, but this proposal is disputed, and other, unrelated proteins have since been identified as the mitochondrial Ca(2+) uniporter. To clarify the role of UCPs in mitochondrial Ca(2+) handling, we down-regulated the expression of the only uncoupling protein of HeLa cells, UCP3, and measured Ca(2+) and ATP levels in the cytosol and in organelles with genetically encoded probes. UCP3 silencing did not alter mitochondrial Ca(2+) uptake in permeabilized cells. In intact cells, however, UCP3 depletion increased mitochondrial ATP production and strongly reduced the cytosolic and mitochondrial Ca(2+) elevations evoked by histamine. The reduced Ca(2+) elevations were due to inhibition of store-operated Ca(2+) entry and reduced depletion of endoplasmic reticulum (ER) Ca(2+) stores. UCP3 depletion accelerated the ER Ca(2+) refilling kinetics, indicating that the activity of sarco/endoplasmic reticulum Ca(2+) (SERCA) pumps was increased. Accordingly, SERCA inhibitors reversed the effects of UCP3 depletion on cytosolic, ER, and mitochondrial Ca(2+) responses. Our results indicate that UCP3 is not a mitochondrial Ca(2+) uniporter and that it instead negatively modulates the activity of SERCA by limiting mitochondrial ATP production. The effects of UCP3 on mitochondrial Ca(2+) thus reflect metabolic alterations that impact on cellular Ca(2+) homeostasis. The sensitivity of SERCA to mitochondrial ATP production suggests that mitochondria control the local ATP availability at ER Ca(2+) uptake and release sites.
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