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Eggs contain about 200,000 mitochondria that generate adenosine triphosphate and metabolites essential for oocyte development. Mitochondria also integrate metabolism and transcription via metabolites that regulate epigenetic modifiers, but there is no direct evidence linking oocyte mitochondrial function to the maternal epigenome and subsequent embryo development. Here, we have disrupted oocyte mitochondrial function via deletion of the mitochondrial fission factor Drp1. Fission-deficient oocytes exhibit a high frequency of failure in peri- and postimplantation development. This is associated with altered mitochondrial function, changes in the oocyte transcriptome and proteome, altered subcortical maternal complex, and a decrease in oocyte DNA methylation and H3K27me3. Transplanting pronuclei of fertilized Drp1 knockout oocytes to normal ooplasm fails to rescue embryonic lethality. We conclude that mitochondrial function plays a role in establishing the maternal epigenome, with serious consequences for embryo development.
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http://dx.doi.org/10.1126/sciadv.abl8070 | DOI Listing |
EMBO J
September 2025
Department of Nutritional Sciences and Toxicology, University of California, Berkeley, CA, 94720, USA.
A variety of stressors, including environmental insults, pathological conditions, and transition states, constantly challenge cells that, in turn, activate adaptive responses to maintain homeostasis. Mitochondria have pivotal roles in orchestrating these responses that influence not only cellular energy production but also broader physiological processes. Mitochondria contribute to stress adaptation through mechanisms including induction of the mitochondrial unfolded protein response (UPR) and the integrated stress response (ISR).
View Article and Find Full Text PDFCommun Biol
September 2025
Division of Neurobiology, Faculty of Biology, Ludwig-Maximilians-Universität München, Planegg - Martinsried, Germany.
The internal resistance of axons to ionic current flow determines action potential conduction velocity. Although mitochondria support axonal function, axons have been modeled as organelle-free cables, and mitochondrial impact on conduction velocity, specifically by increasing internal resistance, remains understudied. We combine computational modeling and electron microscopy of forebrain premotor axons controlling birdsong production.
View Article and Find Full Text PDFNat Metab
September 2025
Cellular and Molecular Physiology Department, Yale School of Medicine, New Haven, CT, USA.
The essential cofactor coenzyme A (CoASH) and its thioester derivatives (acyl-CoAs) have pivotal roles in cellular metabolism. However, the mechanism by which different acyl-CoAs are accurately partitioned into different subcellular compartments to support site-specific reactions, and the physiological impact of such compartmentalization, remain poorly understood. Here, we report an optimized liquid chromatography-mass spectrometry-based pan-chain acyl-CoA extraction and profiling method that enables a robust detection of 33 cellular and 23 mitochondrial acyl-CoAs from cultured human cells.
View Article and Find Full Text PDFCell Death Dis
September 2025
Department of Endocrinology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, 510080, China.
In recent years, there has been a rapid increase in the incidence of thyroid carcinoma (TC). Our study focuses on the regulatory effect of circular RNAs on metabolism of TC, aiming to provide new insights into the mechanisms of progression and a potential therapeutic target for TC. In this study, we identified high expression levels of circPSD3 in TC tissues through RNA sequencing.
View Article and Find Full Text PDFPhysiol Plant
September 2025
Department of Plant Physiology, Institute of Biology, Martin-Luther-Universität Halle-Wittenberg, Halle (Saale), Germany.
Several genes in the mitochondria of angiosperms are interrupted by introns, and their posttranscriptional excision involves numerous nucleus-encoded auxiliary factors. Most of these factors are of eukaryotic origin, among them members of the pentatricopeptide-repeat (PPR) family of RNA-binding proteins. This family divides into the PLS and P classes, with PLS-class proteins typically participating in C-to-U mRNA editing and P-class members contributing to transcript stabilization and intron splicing.
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