ArticleCell death and differentiation2017
Granzyme B enters the mitochondria in a Sam50-, Tim22- and mtHsp70-dependent manner to induce apoptosis.
Article in Cell death and differentiation, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 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
35 citing papers in PubMed, 45 citations in OpenAlex.
- High Expression of SAMM50 Indicates Poor Clinical Prognosis in Hepatocellular Carcinoma and Represents a Potential Novel Biomarker.Biological procedures online · 2026Article
- A review of organoid-immune co-culture platforms to model the immune microenvironment of hepatocellular carcinoma and guide immunotherapy.Journal of translational medicine · 2026Review
- The lncrnas: innovative multifunctional players of drug resistance in colorectal cancer.Cancer cell international · 2025Review
- Ex vivo single-cell profiling of acute myocardial infarction patients reveals disproportionate CD66bBioengineering & translational medicine · 2025Article
- Mitochondrial protein import stress.Nature cell biology · 2025Review
- Review
- Regulated Cell Death Pathways in Pathological Cardiac Hypertrophy.Reviews in cardiovascular medicine · 2024Review
- Ablation of Sam50 is associated with fragmentation and alterations in metabolism in murine and human myotubes.Journal of cellular physiology · 2024Article
- Granzymes in health and diseases: the good, the bad and the ugly.Frontiers in immunology · 2024Review
- Ablation ofbioRxiv : the preprint server for biology · 2023Article
- Fluid shear stress enhances natural killer cell's cytotoxicity toward circulating tumor cells through NKG2D-mediated mechanosensing.APL bioengineering · 2023Article
- Genetic Variation ofInternational journal of molecular sciences · 2022Article
- Apoptosis evasion via long non-coding RNAs in colorectal cancer.Cancer cell international · 2022Review
- Natural killer cells kill extracellular Pseudomonas aeruginosa using contact-dependent release of granzymes B and H.PLoS pathogens · 2022Article
- Is Mitochondrial Oxidative Stress a Viable Therapeutic Target in Preeclampsia?Antioxidants (Basel, Switzerland) · 2022Review
- Bcl-2 Family Members and the Mitochondrial Import Machineries: The Roads to Death.Biomolecules · 2022Review
- Review
- The Diversity of the Mitochondrial Outer Membrane Protein Import Channels: Emerging Targets for Modulation.Molecules (Basel, Switzerland) · 2021Review
- Protein Import Assay into Mitochondria Isolated from Human Cells.Bio-protocol · 2021Article
- Long Non-coding RNA LINC02474 Affects Metastasis and Apoptosis of Colorectal Cancer by Inhibiting the Expression of GZMB.Frontiers in oncology · 2021Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 5 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
We have found that granzyme B (GB)-induced apoptosis also requires reactive oxygen species resulting from the alteration of mitochondrial complex I. How GB, which does not possess a mitochondrial targeting sequence, enter this organelle is unknown. We show that GB enters the mitochondria independently of the translocase of the outer mitochondrial membrane complex, but requires instead Sam50, the central subunit of the sorting and assembly machinery that integrates outer membrane β-barrel proteins. Moreover, GB breaches the inner membrane through Tim22, the metabolite carrier translocase pore, in a mitochondrial heat-shock protein 70 (mtHsp70)-dependent manner. Granzyme A (GA) and caspase-3 use a similar route to the mitochondria. Finally, preventing GB from entering the mitochondria either by mutating lysine 243 and arginine 244 or depleting Sam50 renders cells more resistant to GB-mediated reactive oxygen species and cell death. Similarly, Sam50 depletion protects cells from GA-, GM- and caspase-3-mediated cell death. Therefore, cytotoxic molecules enter the mitochondria to induce efficiently cell death through a noncanonical Sam50-, Tim22- and mtHsp70-dependent import pathway.
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.