Filtered By:
Source: Journal of Biological Chemistry
Condition: Mitochondrial Disease
This page shows you your search results in order of date.
Order by Relevance | Date
Total 25 results found since Jan 2013.
Chronic treatment with the complex I inhibitor MPP+ depletes endogenous PTEN-induced kinase 1 (PINK1) via up-regulation of Bcl-2-associated athanogene 6 (BAG6) Neurobiology
Mitochondrial dysfunction is implicated in sporadic and familial Parkinson's disease (PD). However, the mechanisms that impair homeostatic responses to mitochondrial dysfunction remain unclear. Previously, we found that chronic, low-dose administration of the mitochondrial complex I inhibitor 1-methyl-4-phenylpyridinium (MPP+) dysregulates mitochondrial fission–fusion, mitophagy, and mitochondrial biogenesis. Given that PTEN-induced kinase 1 (PINK1) regulates mitochondrial function, dynamics, and turnover, we hypothesized that alterations in endogenous PINK1 levels contribute to depletion of mitochondria during chronic c...
Source: Journal of Biological Chemistry - June 4, 2020 Category: Chemistry Authors: Manish Verma, Jianhui Zhu, Kent Z. Q. Wang, Charleen T. Chu Tags: Molecular Bases of Disease Source Type: research
The mitochondrial protein PGAM5 suppresses energy consumption in brown adipocytes by repressing expression of uncoupling protein 1 Metabolism
Accumulating evidence suggests that brown adipose tissue (BAT) is a potential therapeutic target for managing obesity and related diseases. PGAM family member 5, mitochondrial serine/threonine protein phosphatase (PGAM5), is a protein phosphatase that resides in the mitochondria and regulates many biological processes, including cell death, mitophagy, and immune responses. Because BAT is a mitochondria-rich tissue, we have hypothesized that PGAM5 has a physiological function in BAT. We previously reported that PGAM5-knockout (KO) mice are resistant to severe metabolic stress. Importantly, lipid accumulation is suppressed i...
Source: Journal of Biological Chemistry - April 23, 2020 Category: Chemistry Authors: Sho Sugawara, Yusuke Kanamaru, Shiori Sekine, Lila Maekawa, Akinori Takahashi, Tadashi Yamamoto, Kengo Watanabe, Takao Fujisawa, Kazuki Hattori, Hidenori Ichijo Tags: Cell Biology Source Type: research
A dual druggable genome-wide siRNA and compound library screening approach identifies modulators of parkin recruitment to mitochondria Molecular Bases of Disease
Genetic and biochemical evidence points to an association between mitochondrial dysfunction and Parkinson's disease (PD). PD-associated mutations in several genes have been identified and include those encoding PTEN-induced putative kinase 1 (PINK1) and parkin. To identify genes, pathways, and pharmacological targets that modulate the clearance of damaged or old mitochondria (mitophagy), here we developed a high-content imaging-based assay of parkin recruitment to mitochondria and screened both a druggable genome-wide siRNA library and a small neuroactive compound library. We used a multiparameter principal component analy...
Source: Journal of Biological Chemistry - March 5, 2020 Category: Chemistry Authors: Helen L. Scott, Nicola Buckner, Francesc Fernandez-Albert, Elisa Pedone, Lorena Postiglione, Gongyu Shi, Nicholas Allen, Liang-Fong Wong, Lorenzo Magini, Lucia Marucci, Gregory A. O'Sullivan, Sarah Cole, Justin Powell, Peter Maycox, James B. Uney Tags: Neurobiology Source Type: research
Complement 1q-like-3 protein inhibits insulin secretion from pancreatic {beta}-cells via the cell adhesion G protein-coupled receptor BAI3 Cell Biology
Secreted proteins are important metabolic regulators in both healthy and disease states. Here, we sought to investigate the mechanism by which the secreted protein complement 1q-like-3 (C1ql3) regulates insulin secretion from pancreatic β-cells, a key process affecting whole-body glucose metabolism. We found that C1ql3 predominantly inhibits exendin-4– and cAMP-stimulated insulin secretion from mouse and human islets. However, to a lesser extent, C1ql3 also reduced insulin secretion in response to KCl, the potassium channel blocker tolbutamide, and high glucose. Strikingly, C1ql3 did not affect insulin secretion stimula...
Source: Journal of Biological Chemistry - November 23, 2018 Category: Chemistry Authors: Rajesh Gupta, Dan C. Nguyen, Michael D. Schaid, Xia Lei, Appakalai N. Balamurugan, G. William Wong, Jeong-a Kim, James E. Koltes, Michelle E. Kimple, Sushant Bhatnagar Tags: Metabolism Source Type: research
The ubiquitin E3 ligase CHIP promotes proteasomal degradation of the serine/threonine protein kinase PINK1 during staurosporine-induced cell death Cell Biology
In this study, we demonstrate that the ubiquitin E3 ligase carboxyl terminus of Hsp70-interacting protein (CHIP) promotes PINK1 ubiquitination and decreases its steady-state levels. Moreover, PINK1 levels were strongly reduced in HEK293 and SH-SY5Y cells exposed to the apoptosis-inducer staurosporine. Of note, we found that this reduction resulted from CHIP-mediated PINK1 ubiquitination. Accordingly, siRNA-mediated CHIP knockdown reduced susceptibility to staurosporine-induced cell death. Taken together, these findings suggest that CHIP plays a role in negative regulation of PINK1 stability and may suppress PINK1's cytopro...
Source: Journal of Biological Chemistry - January 26, 2018 Category: Chemistry Authors: Lang Yoo, Kwang Chul Chung Tags: Protein Synthesis and Degradation Source Type: research
Lactate-mediated mitoribosomal defects impair mitochondrial oxidative phosphorylation and promote hepatoma cell invasiveness Gene Regulation
Impaired mitochondrial oxidative phosphorylation (OXPHOS) capacity, accompanied by enhanced glycolysis, is a key metabolic feature of cancer cells, but its underlying mechanism remains unclear. Previously, we reported that human hepatoma cells that harbor OXPHOS defects exhibit high tumor cell invasiveness via elevated claudin-1 (CLN1). In the present study, we show that OXPHOS-defective hepatoma cells (SNU354 and SNU423 cell lines) exhibit reduced expression of mitochondrial ribosomal protein L13 (MRPL13), a mitochondrial ribosome (mitoribosome) subunit, suggesting a ribosomal defect. Specific inhibition of mitoribosomal ...
Source: Journal of Biological Chemistry - December 8, 2017 Category: Chemistry Authors: Young-Kyoung Lee, Jin J. Lim, Un-woo Jeoun, Seongki Min, Eun-beom Lee, So Mee Kwon, Changhan Lee, Gyesoon Yoon Tags: Molecular Bases of Disease Source Type: research
Overexpression of sphingosine-1-phosphate lyase protects insulin-secreting cells against cytokine toxicity Metabolism
In conclusion, the relatively low endogenous Spl expression level in insulin-secreting cells contributes to their extraordinary vulnerability to proinflammatory cytokine toxicity and may therefore represent a promising target for β-cell protection in type 1 diabetes mellitus.
Source: Journal of Biological Chemistry - December 8, 2017 Category: Chemistry Authors: Claudine Hahn, Karolina Tyka, Julie D. Saba, Sigurd Lenzen, Ewa Gurgul-Convey Tags: Molecular Bases of Disease Source Type: research
Insulin-like growth factor 1 signaling is essential for mitochondrial biogenesis and mitophagy in cancer cells Metabolism
Mitochondrial activity and metabolic reprogramming influence the phenotype of cancer cells and resistance to targeted therapy. We previously established that an insulin-like growth factor 1 (IGF-1)-inducible mitochondrial UTP carrier (PNC1/SLC25A33) promotes cell growth. This prompted us to investigate whether IGF signaling is essential for mitochondrial maintenance in cancer cells and whether this contributes to therapy resistance. Here we show that IGF-1 stimulates mitochondrial biogenesis in a range of cell lines. In MCF-7 and ZR75.1 breast cancer cells, IGF-1 induces peroxisome proliferator–activated receptor γ coac...
Source: Journal of Biological Chemistry - October 13, 2017 Category: Chemistry Authors: Amy Lyons, Michael Coleman, Sarah Riis, Cedric Favre, Ciara H. O'Flanagan, Alexander V. Zhdanov, Dmitri B. Papkovsky, Stephen D. Hursting, Rosemary O'Connor Tags: Molecular Bases of Disease Source Type: research
Mitochondrial Activity in Human White Adipocytes Is Regulated by the Ubiquitin Carrier Protein 9/microRNA-30a Axis Cell Biology
In this study, we demonstrate that the mRNA and protein expression of Ubc9 are regulated by the microRNA miRNA-30a (miR-30a) in human subcutaneous adipocytes. Ubc9 and miR-30a exhibit inverse expression in adipose tissue, with miR-30a robustly elevated in brown fat. Depletion of Ubc9 by siRNA or enforced expression of a miR-30a mimic augments mitochondrial volume and respiration in human white adipocytes, reflecting features of brown fat cells. Furthermore, Ubc9 depletion induces a brown fat gene program in human subcutaneous adipocytes. Induction of the beige-selective gene program corresponds to stabilization of the PR d...
Source: Journal of Biological Chemistry - November 17, 2016 Category: Chemistry Authors: Eun Hee Koh, Yong Chen, David A. Bader, Mark P. Hamilton, Bin He, Brian York, Shingo Kajimura, Sean E. McGuire, Sean M. Hartig Tags: Gene Regulation Source Type: research
MIOX in Diabetic Nephropathy Molecular Bases of Disease
In conclusion, this study highlights a novel mechanism where MIOX under HG ambience exacerbates renal injury during the progression of diabetic nephropathy following the generation of excessive ROS via an unexplored G-X pathway.
Source: Journal of Biological Chemistry - March 11, 2016 Category: Chemistry Authors: Sun, L., Dutta, R. K., Xie, P., Kanwar, Y. S. Tags: Glycobiology and Extracellular Matrices Source Type: research
VDAC1 Mediates A{beta} Cytotoxicity Cell Biology
In this study we demonstrate the involvement of VDAC1 and a VDAC1 N-terminal peptide (VDAC1-N-Ter) in Aβ cell penetration and cell death induction. Aβ directly interacted with VDAC1 and VDAC1-N-Ter, as monitored by VDAC1 channel conductance, surface plasmon resonance, and microscale thermophoresis. Preincubated Aβ interacted with bilayer-reconstituted VDAC1 and increased its conductance ∼2-fold. Incubation of cells with Aβ resulted in mitochondria-mediated apoptotic cell death. However, the presence of non-cell-penetrating VDAC1-N-Ter peptide prevented Aβ cellular entry and Aβ-induced mitochondria-mediated apoptosi...
Source: Journal of Biological Chemistry - December 25, 2015 Category: Chemistry Authors: Smilansky, A., Dangoor, L., Nakdimon, I., Ben-Hail, D., Mizrachi, D., Shoshan-Barmatz, V. Tags: Molecular Bases of Disease Source Type: research
SAMHD1 Activity in dGK Deficiency Molecular Bases of Disease
The dNTP triphosphohydrolase SAMHD1 is a nuclear antiviral host restriction factor limiting HIV-1 infection in macrophages and a major regulator of dNTP concentrations in human cells. In normal human fibroblasts its expression increases during quiescence, contributing to the small dNTP pool sizes of these cells. Down-regulation of SAMHD1 by siRNA expands all four dNTP pools, with dGTP undergoing the largest relative increase. The deoxyguanosine released by SAMHD1 from dGTP can be phosphorylated inside mitochondria by deoxyguanosine kinase (dGK) or degraded in the cytosol by purine nucleoside phosphorylase. Genetic mutation...
Source: Journal of Biological Chemistry - October 23, 2015 Category: Chemistry Authors: Franzolin, E., Salata, C., Bianchi, V., Rampazzo, C. Tags: DNA and Chromosomes Source Type: research
GAPDH Aggregates Promote A{beta} Amyloidogenesis Molecular Bases of Disease
Alzheimer disease (AD) is a progressive neurodegenerative disorder characterized by loss of neurons and formation of pathological extracellular deposits induced by amyloid-β peptide (Aβ). Numerous studies have established Aβ amyloidogenesis as a hallmark of AD pathogenesis, particularly with respect to mitochondrial dysfunction. We have previously shown that glycolytic glyceraldehyde-3-phosphate dehydrogenase (GAPDH) forms amyloid-like aggregates upon exposure to oxidative stress and that these aggregates contribute to neuronal cell death. Here, we report that GAPDH aggregates accelerate Aβ amyloidogenesis and subseque...
Source: Journal of Biological Chemistry - October 23, 2015 Category: Chemistry Authors: Itakura, M., Nakajima, H., Kubo, T., Semi, Y., Kume, S., Higashida, S., Kaneshige, A., Kuwamura, M., Harada, N., Kita, A., Azuma, Y.-T., Yamaji, R., Inui, T., Takeuchi, T. Tags: Neurobiology Source Type: research
Mitochondrially Mediated HSF1 Activation Induces Cln-1 Molecular Bases of Disease
In this study, we demonstrated that mitochondrial respiratory defects induced Cln-1 transcription via reactive oxygen species (ROS)-mediated heat shock factor 1 (HSF1) activation, which contributed to hepatoma invasiveness. We first confirmed the inverse relationship between mitochondrial defects and Cln-1 induction in SNU hepatoma cells and hepatocellular carcinoma tissues. We then examined five different respiratory complex inhibitors, and complex I inhibition by rotenone most effectively induced Cln-1 at the transcriptional level. Rotenone increased both mitochondrial and cytosolic ROS. In addition, rotenone-induced Cln...
Source: Journal of Biological Chemistry - August 28, 2015 Category: Chemistry Authors: Lee, J.-H., Lee, Y.-K., Lim, J. J., Byun, H.-O., Park, I., Kim, G.-H., Xu, W. G., Wang, H.-J., Yoon, G. Tags: Signal Transduction Source Type: research
VDAC2 Regulates Steroidogenesis Membrane Biology
Steroid hormones are essential for carbohydrate metabolism, stress management, and reproduction and are synthesized from cholesterol in mitochondria of adrenal glands and gonads/ovaries. In acute stress or hormonal stimulation, steroidogenic acute regulatory protein (StAR) transports substrate cholesterol into the mitochondria for steroidogenesis by an unknown mechanism. Here, we report for the first time that StAR interacts with voltage-dependent anion channel 2 (VDAC2) at the mitochondria-associated endoplasmic reticulum membrane (MAM) prior to its translocation to the mitochondrial matrix. In the MAM, StAR interacts wit...
Source: Journal of Biological Chemistry - January 28, 2015 Category: Chemistry Authors: Prasad, M., Kaur, J., Pawlak, K. J., Bose, M., Whittal, R. M., Bose, H. S. Tags: Molecular Bases of Disease Source Type: research
