A5054452204- Autophagy in Disease and Therapy
- Mitochondrial Function and Pathology
- ATP Synthase and ATPases Research
- Cardiac Ischemia and Reperfusion
- Cell death mechanisms and regulation
- Adipose Tissue and Metabolism
- Calcium signaling and nucleotide metabolism
- RNA modifications and cancer
- Parkinson's Disease Mechanisms and Treatments
- Extracellular vesicles in disease
- Ubiquitin and proteasome pathways
- Endoplasmic Reticulum Stress and Disease
- Sirtuins and Resveratrol in Medicine
- Metabolism and Genetic Disorders
- RNA Interference and Gene Delivery
- Receptor Mechanisms and Signaling
- Lipid metabolism and biosynthesis
- Peptidase Inhibition and Analysis
- MicroRNA in disease regulation
- Congenital heart defects research
- Nitric Oxide and Endothelin Effects
- Cancer Mechanisms and Therapy
- Calpain Protease Function and Regulation
- Cellular transport and secretion
- Tissue Engineering and Regenerative Medicine
University of Montana
2014-2025
University of California, San Diego
2016-2025
Washington University in St. Louis
2018
Linköping University Hospital
2018
Albert Einstein College of Medicine
2015-2017
Université de Montréal
2015
University of Washington
2015
Sanford Burnham Prebys Medical Discovery Institute
2014-2015
University of California, Davis
2015
Rush University Medical Center
2015
The Bcl2/adenovirus E1B 19-kDa interacting protein 3 (Bnip3) is an atypical BH3-only that associated with mitochondrial dysfunction and cell death. Bnip3 also a potent inducer of autophagy, in this study we have investigated the mechanisms by which induces autophagy cardiac myocytes. We found induced translocation dynamin-related 1 (Drp1), involved fission adult Drp1-mediated correlated increased inhibition Drp1 reduced Bnip3-mediated autophagy. Overexpression Drp1K38E, dominant negative...
Cell-based therapies represent a very promising strategy to repair and regenerate the injured heart prevent progression failure. To date, these have had limited success due lack of survival retention infused cells. Therefore, it is important increase our understanding biology cells utilize this information enhance their function in heart. Mitochondria are critical for progenitor cell survival. Here, we demonstrate importance mitochondrial autophagy, or mitophagy, differentiation process...
Myeloid cell leukemia-1 (MCL-1) is an anti-apoptotic BCL-2 protein that up-regulated in several human cancers. MCL-1 also highly expressed myocardium, but its function myocytes has not been investigated. We generated inducible, cardiomyocyte-specific Mcl-1 knockout mice and found ablation of the adult heart led to rapid cardiomyopathy death. Although known inhibit apoptosis, this process was activated MCL-1-deficient hearts. Ultrastructural analysis revealed disorganized sarcomeres swollen...
Rationale: The role of Parkin in hearts is unclear. Germ-line knockout mice have normal hearts, but protective cardiac ischemia. Parkin-mediated mitophagy reportedly either irrelevant, or a major factor, the lethal cardiomyopathy evoked by myocyte–specific interruption dynamin-related protein 1 (Drp1)-mediated mitochondrial fission. Objective: To understand and fission–defective adult mouse hearts. Methods Results: mRNA were present at low levels upregulated after myocyte–directed Drp1 gene...
Abstract Damaged mitochondria pose a lethal threat to cells that necessitates their prompt removal. The currently recognized mechanism for disposal of is autophagy, where damaged organelles are marked via ubiquitylation by Parkin. Here we report novel pathway mitochondrial elimination, in which these undergo Parkin-dependent sequestration into Rab5-positive early endosomes the ESCRT machinery. Following maturation, deliver lysosomes degradation. Although this endosomal activated stressors...
Abstract Mitochondrial quality control is critical for cardiac homeostasis as these organelles are responsible generating most of the energy needed to sustain contraction. Dysfunctional mitochondria normally degraded via intracellular degradation pathways that converge on lysosome. Here, we identified an alternative mechanism eliminate when lysosomal function compromised. We show inhibition leads increased secretion in large extracellular vesicles (EVs). The EVs produced multivesicular...
Bnip3 is a pro-apoptotic BH3-only protein which associated with mitochondrial dysfunction and cell death. also potent inducer of autophagy in many cells. In this study, we have investigated the mechanism by induces adult cardiac myocytes. Overexpression induced extensive Fluorescent microscopy studies ultrastructural analysis revealed selective degradation mitochondria myocytes overexpressing Bnip3. Oxidative stress increased levels intracellular Ca(2+) been reported others to induce...
Background— The anthracycline doxorubicin is an effective chemotherapeutic agent used to treat pediatric cancers but associated with cardiotoxicity that can manifest many years after the initial exposure. To date, very little known about mechanism of this late-onset cardiotoxicity. Methods and Results— understand problem, we developed a model doxorubicin-induced in which juvenile mice were exposed doxorubicin, using cumulative dose did not induce acute These normally had no obvious cardiac...
Bnip3 is a pro-apoptotic member of the Bcl-2 family that down-regulated in pancreatic cancers, which correlates with resistance to chemotherapy and worsened prognosis. In contrast, up-regulated heart failure contributes loss myocardial cells during I/R (ischaemia/reperfusion). exerts its action at mitochondria, but mechanism by mediates mitochondrial dysfunction not clear. present study, we have identified Bax Bak as downstream effectors Bnip3-mediated dysfunction. plays role...
Bcl-2/adenovirus E1B 19-kDa protein-interacting protein 3 (Bnip3) is a member of the Bcl-2 homology domain 3-only subfamily proapoptotic proteins and associated with cell death in myocardium. In this study, we investigated potential mechanism(s) by which Bnip3 activity regulated. We found that forms DTT-sensitive homodimer increased after myocardial ischemia-reperfusion (I/R). The presence antioxidant N-acetylcysteine reduced I/R-induced homodimerization Bnip3. Overexpression cells revealed...