ATAD1 prevents clogging of TOM and damage caused by un-imported mitochondrial proteins

Cell Reports, Journal Year: 2024, Volume and Issue: 43(8), P. 114473 - 114473

Published: July 17, 2024

Language: Английский

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Regulation of FSP1 Myristoylation by NADPH: A Novel Mechanism for Ferroptosis Inhibition

Redox Biology, Journal Year: 2024, Volume and Issue: 73, P. 103176 - 103176

Published: April 30, 2024

Excitotoxicity is a prevalent pathological event in neurodegenerative diseases. The involvement of ferroptosis the pathogenesis excitotoxicity remains elusive. Transcriptome analysis has revealed that cytoplasmic reduced nicotinamide adenine dinucleotide phosphate (NADPH) levels are associated with susceptibility to ferroptosis-inducing compounds. Here we show exogenous NADPH, besides being reductant, interacts N-myristoyltransferase 2 (NMT2) and upregulates N-myristoylated suppressor protein 1 (FSP1). NADPH increases membrane-localized FSP1 strengthens resistance ferroptosis. Arg-291 NMT2 critical for NADPH-NMT2-FSP1 axis-mediated suppression This study suggests plays pivotal role by bridging neuronal We propose mechanism which regulates N-myristoylation, important implications disease treatment.

Language: Английский

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Regulation of proteostasis and innate immunity via mitochondria-nuclear communication

The Journal of Cell Biology, Journal Year: 2024, Volume and Issue: 223(3)

Published: Feb. 9, 2024

Mitochondria are perhaps best known as the “powerhouse of cell” for their role in ATP production required numerous cellular activities. have emerged an important signaling organelle. Here, we first focus on pathways mediated by mitochondria-nuclear communication that promote protein homeostasis (proteostasis). We examine mitochondrial unfolded response (UPRmt) C. elegans, which is regulated a transcription factor harboring both mitochondrial- and nuclear-targeting sequence, integrated stress mammals, well regulation chromatin metabolites. In second section, explore mitochondria-to-nuclear innate immunity inflammation. Perhaps related to prokaryotic origin, mitochondria harbor molecules also found viruses bacteria. If these accumulate cytosol, they elicit same immune responses viral or bacterial infection.

Language: Английский

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Inhibition of mammalian mtDNA transcription acts paradoxically to reverse diet-induced hepatosteatosis and obesity

Nature Metabolism, Journal Year: 2024, Volume and Issue: 6(6), P. 1024 - 1035

Published: April 30, 2024

Abstract The oxidative phosphorylation system 1 in mammalian mitochondria plays a key role transducing energy from ingested nutrients 2 . Mitochondrial metabolism is dynamic and can be reprogrammed to support both catabolic anabolic reactions, depending on physiological demands or disease states. Rewiring of mitochondrial intricately linked metabolic diseases promotes tumour growth 3–5 Here, we demonstrate that oral treatment with an inhibitor transcription (IMT) 6 shifts whole-animal towards fatty acid oxidation, which, turn, leads rapid normalization body weight, reversal hepatosteatosis restoration normal glucose tolerance male mice high-fat diet. Paradoxically, the IMT causes severe reduction capacity concomitant marked upregulation oxidation liver, as determined by proteomics metabolomics analyses. complex I, main dehydrogenase feeding electrons into ubiquinone (Q) pool, whereas levels electron transfer flavoprotein other dehydrogenases connected Q pool are increased. This rewiring caused reduced mtDNA expression liver provides principle for drug obesity obesity-related pathology.

Language: Английский

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Is mitochondrial morphology important for cellular physiology?

Trends in Endocrinology and Metabolism, Journal Year: 2024, Volume and Issue: 35(10), P. 854 - 871

Published: June 12, 2024

Language: Английский

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