Mitochondrial DNA encodes 13 subunits of the oxidative phosphorylation (OXPHOS) system, which are synthesized inside the organelle and essential for cellular energy supply. How mitochondrial gene expression is regulated and integrated into cellular physiology is little understood. Here, we perform a high-throughput screen combining fluorescent labeling of mitochondrial translation products with small interfering RNA (siRNA)-mediated knockdown to identify cellular kinases regulating translation. As proof of principle, the screen identifies known kinases that affect mitochondrial translation, and it also reveals several kinases not yet linked to this process. Among the latter, we focus on the primarily cytosolic kinase, fructosamine 3 kinase (FN3K), which localizes partially to the mitochondria to support translation. FN3K interacts with the mitochondrial ribosome and modulates its assembly, thereby affecting translation. Overall, our work provides a reliable approach to identify protein functions for mitochondrial gene expression in a high-throughput manner.
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http://dx.doi.org/10.1016/j.celrep.2024.115143 | DOI Listing |
Sci Transl Med
March 2025
Clinical Neuroscience Research Center, Department of Neurosurgery and Neurology, Tulane University School of Medicine, New Orleans, LA 70112, USA.
Traumatic brain injury (TBI) rapidly triggers proinflammatory activation of microglia, contributing to secondary brain damage post-TBI. Although the governing role of energy metabolism in shaping the inflammatory phenotype and function of immune cells has been increasingly recognized, the specific alterations in microglial bioenergetics post-TBI remain poorly understood. Itaconate, a metabolite produced by the enzyme aconitate decarboxylase 1 [IRG1; encoded by immune responsive gene 1 ()], is a pivotal metabolic regulator in immune cells, particularly in macrophages.
View Article and Find Full Text PDFJ Immunol
February 2025
Friedrich-Loeffler-Institut, Federal Research Institute for Animal Health, Institute of Immunology, Greifswald-Isle of Riems, Germany.
African swine fever virus (ASFV) is a large DNA virus of the Asfarviridae family that causes a fatal hemorrhagic disease in domestic swine and wild boar. Infections with moderately virulent strains predominantly result in a milder clinical course and lower lethality. As target cells of ASFV, monocytes play a crucial role in triggering T-cell-mediated immune defense and ASF pathogenesis.
View Article and Find Full Text PDFPhysiol Genomics
March 2025
Institute of Biomedical Problems, Russian Academy of Sciences (Moscow, Russia).
Muscle disuse results in complex signaling alterations followed by structural and functional changes, such as atrophy, force decrease and slow-to-fast fiber-type shift. Little is known about human skeletal muscle signaling alterations under long-term muscle disuse. In this study, we describe the effects of 21-day dry immersion on human postural soleus muscle.
View Article and Find Full Text PDFAdv Biol (Weinh)
March 2025
Medizinisches Proteom-Center, Medical Faculty, Ruhr-University Bochum, 44801, Bochum, Germany.
Aging is a progressive and irreversible process, serving as the primary risk factor for neurodegenerative disorders. This study aims to identify the molecular mechanisms underlying physiological aging within the substantia nigra, which is primarily affected by Parkinson's disease, and to draw potential conclusions on the earliest events leading to neurodegeneration in this specific brain region. The characterization of essential stages in aging progress can enhance knowledge of the mechanisms that promote the development of Parkinson's disease.
View Article and Find Full Text PDFJ Cell Sci
March 2025
BRIC-National Centre for Cell Science, S.P. Pune University Campus, Ganeshkhind, Pune-411007, India.
P-bodies (PBs) and stress granules (SGs) are conserved, non-membranous cytoplasmic condensates of RNA-protein complexes. PBs are implicated in post-transcriptional regulation of gene expression through mRNA decay, translational repression and/or storage. Although much is known about the de novo formation of PBs and SGs involving liquid-liquid phase separation through multiple protein-protein and protein-RNA interactions, their subcellular localization and turnover mechanisms are less understood.
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