The packaging of mitochondrial DNA (mtDNA) into DNA-protein assemblies called nucleoids provides an efficient segregating unit of mtDNA, coordinating mtDNA's involvement in cellular metabolism. From the early discovery of mtDNA as "extranuclear" genetic material, its organization into nucleoids and integration into both the mitochondrial organellar network and the cell at large via a variety of signal transduction pathways, mtDNA is a crucial component of the cell's homeostatic network. The mitochondrial nucleoid is composed of a set of DNA-binding core proteins involved in mtDNA maintenance and transcription, and a range of peripheral factors, which are components of signaling pathways controlling mitochondrial biogenesis, metabolism, apoptosis, and retrograde mitochondria-to-nucleus signaling. The molecular interactions of nucleoid components with the organellar network and cellular signaling pathways provide exciting clues to the dynamic integration of mtDNA into cellular metabolic homeostasis.
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http://dx.doi.org/10.1101/cshperspect.a011080 | DOI Listing |
Noncoding RNA Res
April 2025
Kresge Eye Institute, Wayne State University, Detroit, MI, USA.
Diabetic retinopathy, a microvascular complication of diabetes, is the leading cause of blindness in adults, but the molecular mechanism of its development remains unclear. Retinal mitochondrial DNA is damaged and hypermethylated, and mtDNA-encoded genes are downregulated. Expression of a long noncoding RNA (larger than 200 nucleotides, which does not translate into proteins), encoded by mtDNA, cytochrome B (Lnc), is also downregulated.
View Article and Find Full Text PDFProc Jpn Acad Ser B Phys Biol Sci
January 2025
Department of Biological Sciences, Graduate School of Science, The University of Tokyo, Tokyo, Japan.
Cell proliferation is a fundamental characteristic of organisms, driven by the holistic functions of multiple proteins encoded in the genome. However, the individual contributions of thousands of genes and the millions of protein molecules they express to cell proliferation are still not fully understood, even in simple eukaryotes. Here, we present a genome-wide translation map of cells during proliferation in the unicellular alga Cyanidioschyzon merolae, based on the sequencing of ribosome-protected messenger RNA fragments.
View Article and Find Full Text PDFCell Death Dis
November 2024
Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Santiago, Chile.
Optic atrophy protein 1 (OPA1) mediates inner mitochondrial membrane (IMM) fusion and cristae organization. Mutations in OPA1 cause autosomal dominant optic atrophy (ADOA), a leading cause of blindness. Cells from ADOA patients show impaired mitochondrial fusion, cristae structure, bioenergetic function, and mitochondrial DNA (mtDNA) integrity.
View Article and Find Full Text PDFNucleic Acids Res
December 2024
Department of Chemistry, University of California, Riverside, CA 92521, USA.
Mitochondrial DNA (mtDNA) is indispensable for mitochondrial function and is maintained by DNA repair, turnover, mitochondrial dynamics and mitophagy, along with the inherent redundancy of mtDNA. Base excision repair (BER) is a major DNA repair mechanism in mammalian mitochondria. Mitochondrial BER enzymes are implicated in mtDNA-mediated immune response and inflammation.
View Article and Find Full Text PDFNat Cell Biol
December 2024
Department of Genetics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.
Fragile X messenger ribonucleoprotein (FMRP) is a critical regulator of translation, whose dysfunction causes fragile X syndrome. FMRP dysfunction disrupts mitochondrial health in neurons, but it is unclear how FMRP supports mitochondrial homoeostasis. Here we demonstrate that FMRP granules are recruited to the mitochondrial midzone, where they mark mitochondrial fission sites in axons and dendrites.
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