scholarly journals SAMM50 acts with p62 in piecemeal basal- and OXPHOS-induced mitophagy of SAM and MICOS components

2021 ◽  
Vol 220 (8) ◽  
Author(s):  
Yakubu Princely Abudu ◽  
Birendra Kumar Shrestha ◽  
Wenxin Zhang ◽  
Anthimi Palara ◽  
Hanne Britt Brenne ◽  
...  
Keyword(s):  
Quality Control ◽  
Oxidative Phosphorylation ◽  
Contact Site ◽  
Metabolic Switch ◽  
Complex Protein ◽  
Lir Motif

Mitophagy is the degradation of surplus or damaged mitochondria by autophagy. In addition to programmed and stress-induced mitophagy, basal mitophagy processes exert organelle quality control. Here, we show that the sorting and assembly machinery (SAM) complex protein SAMM50 interacts directly with ATG8 family proteins and p62/SQSTM1 to act as a receptor for a basal mitophagy of components of the SAM and mitochondrial contact site and cristae organizing system (MICOS) complexes. SAMM50 regulates mitochondrial architecture by controlling formation and assembly of the MICOS complex decisive for normal cristae morphology and exerts quality control of MICOS components. To this end, SAMM50 recruits ATG8 family proteins through a canonical LIR motif and interacts with p62/SQSTM1 to mediate basal mitophagy of SAM and MICOS components. Upon metabolic switch to oxidative phosphorylation, SAMM50 and p62 cooperate to mediate efficient mitophagy.

scholarly journals Wild-Type p53 Promotes Cancer Metabolic Switch by Inducing PUMA-Dependent Suppression of Oxidative Phosphorylation

Cancer Cell ◽  
2019 ◽  
Vol 35 (2) ◽  
pp. 191-203.e8 ◽  
Author(s):  
Jinchul Kim ◽  
Lili Yu ◽  
Wancheng Chen ◽  
Yanxia Xu ◽  
Meng Wu ◽  
...  
Keyword(s):  
Oxidative Phosphorylation ◽  
Wild Type ◽  
Metabolic Switch ◽  
Wild Type P53

scholarly journals ITGB2-mediated metabolic switch in CAFs promotes OSCC proliferation by oxidation of NADH in mitochondrial oxidative phosphorylation system

Theranostics ◽  
2020 ◽  
Vol 10 (26) ◽  
pp. 12044-12059
Author(s):  
Xiaoxin Zhang ◽  
Yingchun Dong ◽  
Mengxiang Zhao ◽  
Liang Ding ◽  
Xihu Yang ◽  
...  
Keyword(s):  
Oxidative Phosphorylation ◽  
Mitochondrial Oxidative Phosphorylation ◽  
Metabolic Switch ◽  
Oxidative Phosphorylation System

scholarly journals Disrupted in schizophrenia 1 (DISC1) is a constituent of the mammalian mitochondrial contact site and cristae organizing system (MICOS) complex, and is essential for oxidative phosphorylation

2016 ◽  
Vol 25 (19) ◽  
pp. 4157-4169 ◽  
Author(s):  
Estefanía Piñero-Martos ◽  
Bernardo Ortega-Vila ◽  
Josep Pol-Fuster ◽  
Eugenia Cisneros-Barroso ◽  
Laura Ruiz-Guerra ◽  
...  
Keyword(s):  
Oxidative Phosphorylation ◽  
Contact Site

scholarly journals Oxidative switch drives mitophagy defects in dopaminergic parkin mutant patient neurons

2020 ◽  
Author(s):  
Aurelie Schwartzentruber ◽  
Camilla Boschian ◽  
Fernanda Martins Lopes ◽  
Monika A Myszczynska ◽  
Elizabeth J New ◽  
...  
Keyword(s):  
Oxidative Phosphorylation ◽  
Progenitor Cells ◽  
Dopaminergic Neurons ◽  
Neuronal Morphology ◽  
Fluorescent Imaging ◽  
Mitochondrial Morphology ◽  
Metabolic Switch ◽  
Mitochondrial Abnormalities ◽  
Neuronal Progenitor Cells ◽  
Neuronal Progenitor

AbstractBackground Mutations in parkin are the most common cause of early onset Parkinson’s disease. Parkin is an E3 ubiquitin ligase, functioning in mitophagy. Mitochondrial abnormalities are present in parkin mutant models. Patient derived neurons are a promising model in which to study pathogenic mechanisms and therapeutic targets. Here we generate induced neuronal progenitor cells from parkin mutant patient fibroblasts with a high dopaminergic neuron yield. We reveal changing mitochondrial phenotypes as neurons undergo a metabolic switch during differentiation. Methods Fibroblasts from 4 controls and 4 parkin mutant patients were transformed into induced neuronal progenitor cells and subsequently differentiated into dopaminergic neurons. Mitochondrial morphology, function and mitophagy were evaluated using live cell fluorescent imaging, cellular ATP and reactive oxygen species production quantification. Results Direct conversion of control and parkin mutant patient fibroblasts results in induced neuronal progenitor and their differentiation yields high percentage of dopaminergic neurons. We were able to observe changing mitochondrial phenotypes as neurons undergo a metabolic switch during differentiation. Our results show that when pre-neurons are glycolytic early in differentiation mitophagy is unimpaired by PRKN deficiency. However as neurons become oxidative phosphorylation dependent, mitophagy is severely impaired in the PRKN mutant patient neurons. These changes correlate with changes in mitochondrial function and morphology; resulting in lower neuron yield and altered neuronal morphology. Conclusions Induced neuronal progenitor cell conversion can produce a high yield of dopaminergic neurons. The mitochondrial phenotype, including mitophagy status, is highly dependent on the metabolic status of the cell. Only when neurons are oxidative phosphorylation reliant the extent of mitochondrial abnormalities are identified. These data provide insight into cell specific effects of PRKN mutations, in particular in relation to mitophagy dependent disease phenotypes and provide avenues for alternative therapeutic approaches.

scholarly journals HIF-1α Is a Metabolic Switch between Glycolytic-Driven Migration and Oxidative Phosphorylation-Driven Immunosuppression of Tregs in Glioblastoma

Cell Reports ◽  
2019 ◽  
Vol 27 (1) ◽  
pp. 226-237.e4 ◽  
Author(s):  
Jason Miska ◽  
Catalina Lee-Chang ◽  
Aida Rashidi ◽  
Megan E. Muroski ◽  
Alan L. Chang ◽  
...  
Keyword(s):  
Oxidative Phosphorylation ◽  
Metabolic Switch

scholarly journals RNAase III-Type Enzyme Dicer Regulates Mitochondrial Fatty Acid Oxidative Metabolism in Cardiac Mesenchymal Stem Cells

2019 ◽  
Vol 20 (22) ◽  
pp. 5554 ◽  
Author(s):  
Xuan Su ◽  
Yue Jin ◽  
Yan Shen ◽  
Il-man Kim ◽  
Neal L. Weintraub ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Oxidative Phosphorylation ◽  
Oxidative Metabolism ◽  
Gene Deletion ◽  
Aerobic Glycolysis ◽  
Critical Role ◽  
Mitochondrial Oxidative Phosphorylation ◽  
Metabolic Switch ◽  
Mitochondrial Fatty Acid

Cardiac mesenchymal stem cells (C-MSC) play a key role in maintaining normal cardiac function under physiological and pathological conditions. Glycolysis and mitochondrial oxidative phosphorylation predominately account for energy production in C-MSC. Dicer, a ribonuclease III endoribonuclease, plays a critical role in the control of microRNA maturation in C-MSC, but its role in regulating C-MSC energy metabolism is largely unknown. In this study, we found that Dicer knockout led to concurrent increase in both cell proliferation and apoptosis in C-MSC compared to Dicer floxed C-MSC. We analyzed mitochondrial oxidative phosphorylation by quantifying cellular oxygen consumption rate (OCR), and glycolysis by quantifying the extracellular acidification rate (ECAR), in C-MSC with/without Dicer gene deletion. Dicer gene deletion significantly reduced mitochondrial oxidative phosphorylation while increasing glycolysis in C-MSC. Additionally, Dicer gene deletion selectively reduced the expression of β-oxidation genes without affecting the expression of genes involved in the tricarboxylic acid (TCA) cycle or electron transport chain (ETC). Finally, Dicer gene deletion reduced the copy number of mitochondrially encoded 1,4-Dihydronicotinamide adenine dinucleotide (NADH): ubiquinone oxidoreductase core subunit 6 (MT-ND6), a mitochondrial-encoded gene, in C-MSC. In conclusion, Dicer gene deletion induced a metabolic shift from oxidative metabolism to aerobic glycolysis in C-MSC, suggesting that Dicer functions as a metabolic switch in C-MSC, which in turn may regulate proliferation and environmental adaptation.

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