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Dysfunctional BCAA degradation triggers neuronal damage through disrupted AMPK-mitochondrial axis due to enhanced PP2Ac interaction.
Commun Biol
January 2025
National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Zhunan, 350401, Taiwan.
Metabolic and neurological disorders commonly display dysfunctional branched-chain amino acid (BCAA) metabolism, though it is poorly understood how this leads to neurological damage. We investigated this by generating Drosophila mutants lacking BCAA-catabolic activity, resulting in elevated BCAA levels and neurological dysfunction, mimicking disease-relevant symptoms. Our findings reveal a reduction in neuronal AMP-activated protein kinase (AMPK) activity, which disrupts autophagy in mutant brain tissues, linking BCAA imbalance to brain dysfunction.
View Article and Find Full Text PDFExploring the protective role of caffeine against Taraxacum-Induced ribotoxic stress mediated through autophagy and mitochondrial depolarization.
Sci Rep
January 2025
Division of General Surgery, Department of Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei City, 114, Taiwan, Republic of China.
The ribotoxic stress response is a pathway that gets activated when ribosomes get impaired, leading to disruptions in protein synthesis, increased inflammatory signaling, and cell death if left unresolved. Taraxacum can induce apoptosis-associated ribosomal RNA (rRNA) cleavage, however, the exact working mechanism of Taraxacum-induced rRNA cleavage remains unclear. In this study, we used the RNA integrity (RIN) value and 28S/18S ratio to confirm the integrity of experiments.
View Article and Find Full Text PDFMitochondrial DNA variants and their impact on epigenetic and biological aging in young adulthood.
Transl Psychiatry
January 2025
Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, ON, Canada.
The pace of biological aging varies between people independently of chronological age and mitochondria dysfunction is a key hallmark of biological aging. We hypothesized that higher functional impact (FI) score of mitochondrial DNA (mtDNA) variants might contribute to premature aging and tested the relationships between a novel FI score of mtDNA variants and epigenetic and biological aging in young adulthood. A total of 81 participants from the European Longitudinal Study of Pregnancy and Childhood (ELSPAC) prenatal birth cohort had good quality genetic data as well as blood-based markers to estimate biological aging in the late 20.
View Article and Find Full Text PDFBiotin mitigates the development of manganese-induced, Parkinson's disease-related neurotoxicity in and human neurons.
Sci Signal
January 2025
Department of Environmental Medicine, University of Rochester School of Medicine and Dentistry, Rochester, NY 14642, USA.
Chronic exposure to manganese (Mn) induces manganism and has been widely implicated as a contributing environmental factor to Parkinson's disease (PD), featuring notable overlaps between the two in motor symptoms and clinical hallmarks. Here, we developed an adult model of Mn toxicity that recapitulated key parkinsonian features, spanning behavioral deficits, neuronal loss, and dysfunctions in lysosomes and mitochondria. Metabolomics analysis of the brain and body tissues of these flies at an early stage of toxicity identified systemic changes in the metabolism of biotin (also known as vitamin B) in Mn-treated groups.
View Article and Find Full Text PDFAbnormalities in mitochondrial energy metabolism induced by cryopreservation negatively affect goat sperm motility.
Front Vet Sci
January 2025
Farm Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan Province, College of Animal Science and Technology, Sichuan Agricultural University, Chengdu, China.
The motility of sperm decreases following cryopreservation, which is closely associated with mitochondrial function. However, the alterations in mitochondrial metabolism after sperm freezing in goats remain unclear. This experiment aimed to investigate the impact of ultra-low temperature freezing on goat sperm's mitochondrial energy metabolism and its potential correlation with sperm motility.
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