Dataset Information

Phosphorylation-dependent mitochondrial translocation of MAP4 is an early step in hypoxia-induced apoptosis in cardiomyocytes.

ABSTRACT: Hypoxic or ischemic apoptosis is often tightly associated with the opening of mitochondrial permeability transition pore (mPTP); however, the molecular mechanisms regulating mPTP and thus mitochondrial-dependent apoptosis remain elusive. Emerging evidence indicates that the movement of key proteins in or out of mitochondria play a critical regulatory role in apoptosis. Here, we reported that, unexpectedly, the microtubule-associated protein 4 (MAP4) translocated from cytosol to mitochondria upon phosphorylation after hypoxia treatment in neonatal cardiomyocytes. When targeted to mitochondria, MAP4 was found to lead to mPTP opening and induce apoptosis. Mitochondrial accumulation and pro-apoptotic function of MAP4 could be reversed through the genetic inhibition of MAP4 phosphorylation. The MAP4(Ala) mutant, which mimicked the dephosphorylated form, suppressed mitochondrial translocation and apoptosis. Our data reveal a novel role of MAP4 in cardiac apoptosis and suggest a potential therapeutic strategy targeting mitochondrial translocation of MAP4 against apoptotic heart diseases.

SUBMITTER: Hu J

PROVIDER: S-EPMC4540186 | biostudies-literature | 2014 Sep

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Phosphorylation-dependent mitochondrial translocation of MAP4 is an early step in hypoxia-induced apoptosis in cardiomyocytes.

Hu J J Chu Z Z Han J J Zhang Q Q Zhang D D Dang Y Y Ren J J Chan H C HC Zhang J J Huang Y Y

Cell death & disease 20140918

Hypoxic or ischemic apoptosis is often tightly associated with the opening of mitochondrial permeability transition pore (mPTP); however, the molecular mechanisms regulating mPTP and thus mitochondrial-dependent apoptosis remain elusive. Emerging evidence indicates that the movement of key proteins in or out of mitochondria play a critical regulatory role in apoptosis. Here, we reported that, unexpectedly, the microtubule-associated protein 4 (MAP4) translocated from cytosol to mitochondria upon ...[more]

PMID: 25232678

Similar Datasets

Project description:The main aim of the present work was to investigate the potential effect of acetone extract of Ficus religosa leaf (FAE) in multiple apoptosis signalling in human breast cancer cells. FAE treatment significantly induced dose and time dependent, irreversible inhibition of breast cancer cell growth with moderate toxicity to normal breast epithelial cells. This observation was validated using Sulforhodamine B assay. Cell cycle analysis by Flow cytometry showed cell cycle arrest in G1 phase and induction of sub-G0 peak. FAE induced chromatin condensation and displayed an increase in apoptotic population in Annexin V-FITC/PI (Fluorescein isothiocyanate/Propidium iodide) double staining. FAE stimulated the loss of mitochondrial membrane potential in multiple breast cancer cell lines when compared to normal diploid cells. To understand the role of Bax in FAE induced apoptosis, we employed a sensitive cell based platform of MCF-7 cells expressing Bax-EGFP. Bax translocation to mitochondria was accompanied by the disruption of mitochondrial membrane potential and marked elevation in LEHDase activity (Caspase 9). Consistent with this data, FAE induced Caspase activation as evidenced by ratio change in FRET Caspase sensor expressing MCF-7 cell line and cleavage of prominent Caspases and PARP. Interestingly, FAE accelerated cell death in a mitochondrial dependent manner in continuous live cell imaging mode indicating its possible photosensitizing effect. Intracellular generation of reactive oxygen species (ROS) by FAE played a critical role in mediating apoptotic cell death and photosensitizing activity. FAE induced dose and time dependent inhibition of cancer cell growth which was associated with Bax translocation and mitochondria mediated apoptosis with the activation of Caspase 9 dependent Caspase cascade. FAE also possessed strong photosensitizing effect on cancer cell line that was mediated through rapid mitochondrial transmembrane potential loss and partial Caspase activation involving generation of intracellular ROS.

Dataset Information

Phosphorylation-dependent mitochondrial translocation of MAP4 is an early step in hypoxia-induced apoptosis in cardiomyocytes.

Publications

Phosphorylation-dependent mitochondrial translocation of MAP4 is an early step in hypoxia-induced apoptosis in cardiomyocytes.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets