ArticleAmerican journal of physiology. Cell physiology2019
Inhibition of the ubiquitous calpains protects complex I activity and enables improved mitophagy in the heart following ischemia-reperfusion.
Article in American journal of physiology. Cell physiology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
45 citing papers in PubMed, 62 citations in OpenAlex.
- Mitofilin Preservation Mitigates Cardiac Injury in Donation-After-Circulatory-Death Hearts.Cells · 2026Article
- Increased Intermembrane Space [CaCirculation research · 2025Article
- Dual Inhibition of PARP and Akt Induces Metabolic Collapse and Apoptosis in Breast Cancer Cells.Cancers · 2025Article
- The potential role of hydrogen sulfide-autophagy axis in diseases.Journal of physiology and biochemistry · 2025Review
- Engineered exosomal miR140 modulates mitophagy of chondrocytes through targeting CAPN1 to alleviate osteoarthritis.Science China. Life sciences · 2025Article
- Calpain inhibition in a transgenic model of calpastatin overexpression facilitates reversal of myocardial hypertrophy.ESC heart failure · 2025Article
- The Role of P53 in Myocardial Ischemia-Reperfusion Injury.Cardiovascular drugs and therapy · 2025Review
- Mitochondrial complex-1 as a therapeutic target for cardiac diseases.Molecular and cellular biochemistry · 2025Review
- Mitochondrial apoptosis in response to cardiac ischemia-reperfusion injury.Journal of translational medicine · 2025Review
- Reducing mitochondrial dysfunction through combination therapy to limit ischemia-reperfusion injury in male DCD rats.Frontiers in cardiovascular medicine · 2025Article
- TRPC6-Calpain-1 Axis Promotes Tubulointerstitial Inflammation by Inhibiting Mitophagy in Diabetic Kidney Disease.Kidney international reports · 2024Article
- Aging-induced mitochondrial dysfunction: two distinct populations of mitochondria versus a combined population.American journal of physiology. Heart and circulatory physiology · 2024Article
- Acute endoplasmic reticulum stress-induced mitochondria respiratory chain damage: The role of activated calpains.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2024Article
- Spinocerebellar ataxias: from pathogenesis to recent therapeutic advances.Frontiers in neuroscience · 2024Review
- Transcriptomics and metabolomics study in mouse kidney of the molecular mechanism underlying energy metabolism response to hypoxic stress in highland areas.Experimental and therapeutic medicine · 2023Article
- Endoplasmic reticulum stress and mitochondrial dysfunction during aging: Role of sphingolipids.Biochimica et biophysica acta. Molecular and cell biology of lipids · 2023Article
- Diet-induced obesity augments ischemic myopathy and functional decline in a murine model of peripheral artery disease.Translational research : the journal of laboratory and clinical medicine · 2023Article
- Matrix metalloproteinase-2 proteolyzes mitofusin-2 and impairs mitochondrial function during myocardial ischemia-reperfusion injury.Basic research in cardiology · 2023Article
- Calpain Regulation and Dysregulation-Its Effects on the Intercalated Disk.International journal of molecular sciences · 2023Review
- Metabolic landscape in cardiac aging: insights into molecular biology and therapeutic implications.Signal transduction and targeted therapy · 2023Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Activation of calpain 1 (CPN1) and calpain 2 (CPN2) contributes to cardiac injury during ischemia (ISC) and reperfusion (REP). Complex I activity is decreased in heart mitochondria following ISC-REP. CPN1 and CPN2 are ubiquitous calpains that exist in both cytosol (cs)-CPN1 and 2 and mitochondria (mit)-CPN1 and 2. Recent work shows that the complex I subunit (NDUFS7) is a potential substrate of the mit-CPN1. We asked whether ISC-REP led to decreased complex I activity via proteolysis of the NDUFS7 subunit via activation of mit-CPN1 and -2. Activation of cs-CPN1 and -2 decreases mitophagy in hepatocytes following ISC-REP. We asked whether activation of cs-CPN1 and -2 impaired mitophagy in the heart following ISC-REP. Buffer-perfused rat hearts underwent 25 min of global ISC and 30 min of REP. MDL-28170 (MDL; 10 µM) was used to inhibit CPN1 and -2. Cytosol, subsarcolemmal mitochondria (SSM), and interfibrillar mitochondria (IFM) were isolated at the end of heart perfusion. Cardiac ISC-REP led to decreased complex I activity with a decrease in the content of NDUFS7 in both SSM and IFM. ISC-REP also resulted in a decrease in cytosolic beclin-1 content, a key component of the autophagy pathway required to form autophagosomes. MDL treatment protected the contents of cytosolic beclin-1 and mitochondrial NDUFS7 in hearts following ISC-REP. These results support that activation of both cytosolic and mitochondrial calpains impairs mitochondria during cardiac ISC-REP. Mitochondria-localized calpains impair complex I via cleavage of a key subunit. Activation of cytosolic calpains contributes to mitochondrial dysfunction by impairing removal of the impaired mitochondria through depletion of a key component of the mitophagy process.
Indexed as
Identifiers
What OpenQuestion holds
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.