Precise regulation of mtDNA transcription and oxidative phosphorylation (OXPHOS) is crucial for human health. As a component of mitochondrial contact site and cristae organizing system (MICOS), Mic60 plays a central role in mitochondrial morphology. However, it remains unclear whether Mic60 affects mitochondrial transcription. Here, we report that Mic60 interacts with mitochondrial transcription factors TFAM and TFB2M. Furthermore, we found that Mic60 knockdown compromises mitochondrial transcription and OXPHOS activities. Importantly, Mic60 deficiency decreased TFAM binding and mitochondrial RNA polymerase (POLRMT) recruitment to the mtDNA promoters. In addition, through mtDNA immunoprecipitation (mIP)-chromatin conformation capture (3C) assays, we found that Mic60 interacted with mtDNA and was involved in the architecture of mtDNA D-loop region. Taken together, our findings reveal a previously unrecognized important role of Mic60 in mtDNA transcription.
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http://dx.doi.org/10.1038/srep07990 | DOI Listing |
Biol Direct
January 2025
Key Laboratory of Geriatrics of Jiangsu Province, Department of Geriatrics, The First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, 210029, Jiangsu, China.
Background: Despite the increasing body of evidence that mitochondrial activities implicate in chronic obstructive pulmonary disease (COPD), we are still far from a causal-logical and mechanistic understanding of the mitochondrial malfunctions in COPD pathogenesis.
Results: Differential expression genes (DEGs) from six publicly available bulk human lung tissue transcriptomic datasets of COPD patients were intersected with the known mitochondria-related genes from MitoCarta3.0 to obtain mitochondria-related DEGs associated with COPD (MitoDEGs).
Commun Biol
January 2025
State Key Laboratory of Swine and Poultry Breeding Industry, College of Animal Science and Technology, Sichuan Agricultural University, Chengdu, Sichuan, P. R. China.
Uncoupling protein 1 (UCP1) is a crucial protein located in the mitochondrial inner membrane that mediates nonshivering thermogenesis. However, the molecular mechanisms by which enhancer-promoter chromatin interactions control Ucp1 transcriptional regulation in brown adipose tissue (BAT) are unclear. Here, we employed circularized chromosome conformation capture coupled with next-generation sequencing (4C-seq) to generate high-resolution chromatin interaction profiles of Ucp1 in interscapular brown adipose tissue (iBAT) and epididymal white adipose tissue (eWAT) and revealed marked changes in Ucp1 chromatin interaction between iBAT and eWAT.
View Article and Find Full Text PDFJ Cell Biol
March 2025
Department of Molecular Biosciences, University of Texas at Austin, Austin, TX, USA.
The interplay between ribosomal protein (RP) composition and mitochondrial function is essential for energy homeostasis. Balanced RP production optimizes protein synthesis while minimizing energy costs, but its impact on mitochondrial functionality remains unclear. Here, we investigated haploinsufficiency for RP genes (rps-10, rpl-5, rpl-33, and rps-23) in Caenorhabditis elegans and corresponding reductions in human lymphoblast cells.
View Article and Find Full Text PDFBackground: Age-related neurodegenerative disorders (NDDs) continuum includes late-onset Alzheimer's disease (LOAD), Dementia with Lewy bodies (DLB), and Parkinson's disease (PD) exhibit shared and distinct clinicopathological characteristics. Each of the different NDDs is characterized by a complex genetic etiology and although numerous loci have been identified via GWAS, and the causal genes and the specific neuronal and glial cell subtypes through which they exert their pathogenic effects are yet to be fully elucidated. We aimed to untangle the genetic complexity of NDDs, and to identify shared and distinct biological pathways and disease driver cell-subtypes across NDDs.
View Article and Find Full Text PDFAlzheimers Dement
December 2024
Nanyang Technological University, Singapore, Singapore.
Background: The mitochondrial translocator protein (TSPO) is a biomarker of inflammation associated with aging and Alzheimer's disease (AD). We have previously shown that TSPO plays a critical role in protective immune responses important in AD. Here we investigated the interaction between TSPO immunomodulatory function and aging in the hippocampus, a region severely affected in AD.
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