ArticleBiophysical journal2013
Characterization of the effect of the mitochondrial protein Hint2 on intracellular Ca(2+) dynamics.
Article in Biophysical journal, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed, 18 citations in OpenAlex.
- HINT2-Mediated Mitochondrial Modulation Contributes to G-CSF Neuroprotection in Alcohol Use Disorder-Related Ischemic Stroke.Molecular neurobiology · 2025Article
- Article
- Protective effect of HINT2 on mitochondrial function via repressing MCU complex activation attenuates cardiac microvascular ischemia-reperfusion injury.Basic research in cardiology · 2021Article
- Identification of an m6A Regulators-Mediated Prognosis Signature For Survival Prediction and Its Relevance to Immune Infiltration in Melanoma.Frontiers in cell and developmental biology · 2021Article
- Advances in the study of cancer metastasis and calcium signaling as potential therapeutic targets.Exploration of targeted anti-tumor therapy · 2021Review
- Acquired Uniparental Disomy Regions Are Associated with Disease Outcome in Patients with Oral Cavity and Oropharynx But Not Larynx Cancers.Translational oncology · 2020Article
- mMolecular cancer · 2019Article
- Interplay Between Intracellular Ca(2+) Oscillations and Ca(2+)-stimulated Mitochondrial Metabolism.Scientific reports · 2016Article
- Optimal microdomain crosstalk between endoplasmic reticulum and mitochondria for Ca2+ oscillations.Scientific reports · 2015Article
Corrections and comments
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Authors and funding
7 authors at 5 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Hint2, one of the five members of the superfamily of the histidine triad AMP-lysine hydrolase proteins, is expressed in mitochondria of various cell types. In human adrenocarcinoma cells, Hint2 modulates Ca(2+) handling by mitochondria. As Hint2 is highly expressed in hepatocytes, we investigated if this protein affects Ca(2+) dynamics in this cell type. We found that in hepatocytes isolated from Hint2(-/-) mice, the frequency of Ca(2+) oscillations induced by 1 μM noradrenaline was 150% higher than in the wild-type. Using spectrophotometry, we analyzed the rates of Ca(2+) pumping in suspensions of mitochondria prepared from hepatocytes of either wild-type or Hint2(-/-) mice; we found that Hint2 accelerates Ca(2+) pumping into mitochondria. We then resorted to computational modeling to elucidate the possible molecular target of Hint2 that could explain both observations. On the basis of a detailed model for mitochondrial metabolism proposed in another study, we identified the respiratory chain as the most probable target of Hint2. We then used the model to predict that the absence of Hint2 leads to a premature opening of the mitochondrial permeability transition pore in response to repetitive additions of Ca(2+) in suspensions of mitochondria. This prediction was then confirmed experimentally.
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