Matrix metalloproteinase‐2 is localized to the mitochondria‐associated membrane in the heart (1154.4)
Bibliographic record
Abstract
Intracellular matrix metalloproteinase‐2 (MMP‐2) is activated by pro‐oxidants to proteolyze intercellular targets. MMP‐2 has recently been reported in mitochondria, a critical source of cellular oxidative stress. However, the methods used to determine MMP‐2 subcellular localization could not differentiate between MMP‐2 in the mitochondria or the mitochondrial‐associated membrane (MAM), a subdomain of the endoplasmic reticulum (ER). We hypothesized that mitochondrial MMP‐2 may be situated in the MAM and therefore investigated the subcellular distribution of MMP‐2. Immunogold electron microscopy revealed MMP‐2 in mitochondria of heart sections from mice. However, HaloTagged MMP‐2 expressed in HL‐1 cardiomyocytes showed an ER‐like distribution with greater colocalization with an ER marker (protein disulfide isomerase) relative to a mitochondrial marker, MitoTracker Red. Although MMP‐2 protein and enzymatic activity were present in crude mitochondrial fractions, once these were separated into purified mitochondria and MAM, MMP‐2 was principally associated with the latter. We also found that calreticulin, an ER and MAM‐resident Ca2+ handling protein and chaperone, could be proteolyzed by MMP‐2 in vitro. Thus, although mitochondria may contain minimal levels of MMP‐2, the majority of MMP‐2 previously identified as “mitochondrial” is in fact associated with the MAM. We hypothesize that MAM‐localized MMP‐2 could affect mitochondrial function by affecting ER‐mitochondrial Ca2+ signaling. Grant Funding Source : Supported by the Canadian Institutes of Health Research
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.002 | 0.001 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".