ArticleAutophagy2012
A cryptic mitochondrial targeting motif in Atg4D links caspase cleavage with mitochondrial import and oxidative stress.
Article in Autophagy, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
What it found
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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
30 citing papers in PubMed, 64 citations in OpenAlex.
- Targeted deletions in human mitochondrial DNA engineered by Type V CRISPR-Cas12a system.NAR molecular medicine · 2025Article
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- Inhibition of miR-542-3p augments autophagy to promote diabetic corneal wound healing.Eye and vision (London, England) · 2024Article
- A High-Throughput Colocalization Pipeline for Quantification of Mitochondrial Targeting across Different Protein Types.ACS synthetic biology · 2023Article
- High-throughput colocalization pipeline quantifies efficacy of mitochondrial targeting signals across different protein types.bioRxiv : the preprint server for biology · 2023Article
- Altered Lysosomal Function Manipulates Cellular Biosynthetic Capacity By Remodeling Intracellular Cholesterol Distribution.Cell biochemistry and biophysics · 2023Article
- Bi-allelic ATG4D variants are associated with a neurodevelopmental disorder characterized by speech and motor impairment.NPJ genomic medicine · 2023Article
- Heme-dependent induction of mitophagy program during differentiation of murine erythroid cells.Experimental hematology · 2023Article
- Life and Death Decisions-The Many Faces of Autophagy in Cell Survival and Cell Death.Biomolecules · 2022Review
- Review
- ATG 4B Serves a Crucial Role in RCE-4-Induced Inhibition of the Bcl-2-Beclin 1 Complex in Cervical Cancer Ca Ski Cells.International journal of molecular sciences · 2021Article
- Dihydromyricetin attenuates palmitic acid-induced oxidative stress by promoting autophagy via SIRT3-ATG4B signaling in hepatocytes.Nutrition & metabolism · 2021Article
- PPARγ/SOD2 Protects Against Mitochondrial ROS-Dependent Apoptosis via Inhibiting ATG4D-Mediated Mitophagy to Promote Pancreatic Cancer Proliferation.Frontiers in cell and developmental biology · 2021Article
- Review
- Review
- Targeting ATG4 in Cancer Therapy.Cancers · 2019Review
- Identification of Kinases and Phosphatases That Regulate ATG4B Activity by siRNA and Small Molecule Screening in Cells.Frontiers in cell and developmental biology · 2018Article
- Article
- AKT-mediated phosphorylation of ATG4B impairs mitochondrial activity and enhances the Warburg effect in hepatocellular carcinoma cells.Autophagy · 2018Article
- Conserved Atg8 recognition sites mediate Atg4 association with autophagosomal membranes and Atg8 deconjugation.EMBO reports · 2017Article
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 3 institutions in 2 countries.
Funding
Abstract
The Atg4 cysteine proteases play crucial roles in the processing of Atg8 proteins during autophagy, but their regulation during cellular stress and differentiation remains poorly understood. We have found that two Atg4 family members--Atg4C and Atg4D--contain cryptic mitochondrial targeting sequences immediately downstream of their canonical (DEVD) caspase cleavage sites. Consequently, caspase-cleaved Atg4D (ΔN63 Atg4D) localizes to the mitochondrial matrix when expressed in mammalian cells, where it undergoes further processing to a ~42 kDa mitochondrial form. Interestingly, caspase cleavage is not needed for Atg4D mitochondrial import, because ~42 kDa mitochondrial Atg4D is observed in cells treated with caspase inhibitors and in cells expressing caspase-resistant Atg4D (DEVA(63)). Using HeLa cell lines stably expressing ΔN63 Atg4D, we showed that mitochondrial Atg4D sensitizes cells to cell death in the presence of the mitochondrial uncoupler, CCCP, and that mitochondrial cristae are less extensive in these cells. We further showed that the organization of mitochondrial cristae is altered during the mitochondrial clearance phase in differentiating primary human erythroblasts stably expressing ΔN63 Atg4D, and that these cells have elevated levels of mitochondrial reactive oxygen species (ROS) during late stages of erythropoiesis. Together these data suggest that the import of Atg4D during cellular stress and differentiation may play important roles in the regulation of mitochondrial physiology, ROS, mitophagy and cell viability.
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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.