Vitamins are vital nutrients essential for metabolism, functioning as coenzymes, antioxidants, and regulators of gene expression. Their absorption and metabolism rely on specialized transport proteins that ensure bioavailability and cellular utilization. Water-soluble vitamins, including B-complex and vitamin C, are transported by solute carrier (SLC) family proteins and ATP-binding cassette (ABC) transporters for efficient uptake and cellular distribution. Fat-soluble vitamins (A, D, E, and K) rely on lipid-mediated pathways through proteins like scavenger receptor class B type I (SR-BI), CD36, and Niemann-Pick C1-like 1 (NPC1L1), integrating their absorption with lipid metabolism. Defective vitamin transporters are associated with diverse metabolic disorders, including neurological, hematological, and mitochondrial diseases. Advances in structural and functional studies of transport proteins highlight their tissue-specific roles and regulatory mechanisms, shedding light on their impact on health and disease. This review emphasizes the significance of vitamin transporters and their potential as therapeutic targets for deficiencies and related chronic conditions.
Yuanyuan Tian, Qi Jia, Meijing Li, Youyang Sia, Pengjing Hu, Kangjing Chen, Ming Li, Xueming Li, Zigang Xu, Lin Ma, Youpi Ye, Ying Lu, Zhucheng Chen·09 Apr 2025
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Nucleosomes are the fundamental unit of chromatin. Chromatin remodeler plays a crucial role in the regulation of gene expression in eukaryotes. It is involved in important physiological processes such as development, immune response and metabolic regulation. During gene expression regulation, chromatin remodelers slide nucleosomes along genomic DNA and play a major role in chromatin organization. Chd1 senses the extranucleosomal linker DNA and controls nucleosome spacing in cells. However, the mechanism of linker DNA sensing by Chd1 is not completely understood. Here we report the cryo-electron microscope (cryoEM) structures of Chd1 engaging nucleosomes in different states. Chd1 induces two exit-DNA conformations, either fully wrapped or partially unwrapped states. Notably, in the unwrapped conformation, the exit DNA interacts with a positively charged loop of the motor, named the exit-DNA binding loop, and traps Chd1 in the closed state in the ATPase cycle, suggesting attenuation of its remodeling activity. Explored single-molecule fluorescence resonance energy transfer (smFRET) and biochemical data supported the regulation of Chd1 remodeling activity by the exit-DNA conformations, which is important for the linker DNA sensitivity. Mutants of the Chd1 exit-DNA binding loop compromised nucleosome organization in yeast cells. Together, our findings provide valuable insights into Chd1 regulation by exit DNA unwrapping. These results provide a new perspective for the study of cell development and metabolism.
Chenhao Xin, Mingcheng Cai, Qianxi Jia, Rong Huang, Rui Li, Junyao Wang, Zi Li, Qiang Zhao, Tianyi Liu, Weidong Zhuang, Jinyu Zhou, Shengxian Li, Yongzhen Tao, Lin Wang, Lifeng Yang·07 Mar 2025
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Diet interventions such as calorie restriction or time-restricted feeding offer potential for weight management, but long-term success is often hindered by poor adherence due to the rewarding effects of sugars. In this study, we demonstrate that sulfur amino acid restriction (SAAR) diets promote rapid fat loss without impairing appetite and physiological locomotion, outperforming diets with restricted branched-chain amino acids. Weekly cycling of SAAR diets preserves metabolic benefits, such as reduced fat mass and improved glucose sensitivity. Metabolic analysis and in vivo isotope tracing revealed a shift towards carbohydrate oxidation in white and brown adipose tissue (WAT and BAT), and liver during the SAAR diet refeeding state, leading to decreased de novo lipogenesis. Enhanced lipolysis and fatty acid oxidation were observed in the heart, brain, BAT, lungs, etc. The reintroduction of methionine or cystine negated these metabolic benefits. Further 13C and 2H tracing experiments indicated that cystine, rather than its derivatives like taurine or H2S, directly regulates adiposity. In a high-fat diet model, SAAR led to sustained fat mass reduction, regardless of the timing of intervention. Additionally, cystine levels correlated positively with body mass index (BMI) and total triglycerides in diabetic patients. Our findings highlight SAAR diet as a promising strategy for long-term weight control by modulating systemic glucose and lipid metabolism homeostasis.
Jack Devine, Anna S Monzel, David Shire, Ayelet M Rosenberg, Alex Junker, Alan A Cohen, Martin Picard·12 Apr 2025
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Energy transformation capacity is generally assumed to be a coherent individual trait driven by genetic and environmental factors. This predicts that some individuals should have consistently high, while others show consistently low mitochondrial oxidative phosphorylation (OxPhos) capacity across organ systems. Here, we test this assumption using multi-tissue molecular and enzymatic assays in mice and humans. Across up to 22 mouse tissues, neither mitochondrial OxPhos capacity nor mitochondrial DNA (mtDNA) density was correlated between tissues (median r = −0.01 to 0.16), indicating that animals with high mitochondrial content or capacity in one tissue may have low content or capacity in other tissues. Similarly, RNA sequencing (RNAseq)-based indices of mitochondrial expression across 45 tissues from 948 women and men (Genotype-Tissue Expression (GTEx)) showed only small to moderate coherence between some tissues, such as between brain regions (r = 0.26), but not between brain-body tissue pairs (r = 0.01). The mtDNA copy number (mtDNAcn) also lacked coherence across human tissues. Mechanistically, tissue-specific differences in mitochondrial gene expression were partially attributable to (ⅰ) tissue-specific activation of energy sensing pathways including the transcriptional coactivator peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1⍺), the integrated stress response (ISR), and other molecular regulators of mitochondrial biology; and (ⅱ) proliferative activity across tissues. Finally, we identify subgroups of individuals with distinct mitochondrial distribution strategies that map onto distinct clinical phenotypes. These data raise the possibility that tissue-specific energy sensing pathways may contribute to idiosyncratic mitochondrial distribution patterns among individuals.
