Atlas of lysosomal aging reveals a metabolite signature shared with lysosomal storage disorders

Lysosomal dysfunction is a well-recognized feature of aging. Here, we used a suite of tools for rapid lysosomal isolation to construct a multitissue atlas of the metabolite changes lysosomes undergo d...

science.org

Sustained loss of Pptc7 triggers variable skeletal muscle dysfunction and diminished body mass through dysregulation of BNIP3

The mitochondrial phosphatase PPTC7 is required to sustain mammalian metabolism, as its global knockout (KO) triggers hypoketotic hypoglycemia and perinatal lethality in mice. However, the extent to w...

doi.org

Extremophiles are rewriting the rules of life on Earth

Creatures that survive extreme conditions like mind-boggling temperatures and toxicity challenge how we define life. Bárbara Pinho finds out how it will impact how we search for life beyond Earth

chemistryworld.com

MTERF1 loss buffers against pathogenic mtDNA deletions through transcriptional regulation

Large-scale mitochondrial DNA (mtDNA) deletions cripple oxidative phosphorylation once they exceed a critical heteroplasmy threshold, causing incurable mitochondrial pathologies. Using a genome-wide C...

biorxiv.org

Nordic track: NIH dysfunction and my Helsinki recruitment

National Institutes of Health aims to prioritize groundbreaking work that challenges existing views with rigor and reproducibility, and shows potential for translation. Increasingly, however, reviewer...

cell.com

Mitochondria directly interact with the nuclear pore complex - Nature

Mitochondria interact directly with the nuclear pore complex via VDAC1–RANBP2 binding to sustain nuclear ATP levels.

nature.com

biorxiv.org

Mechanism of age-related accumulation of mtDNA mutations in human blood - Nature

Genome-wide analyses indicate that accumulation of mitochondrial DNA mutations, a hallmark of ageing, may be caused by cryptic replication errors, which act as passenger mutations that eventually become detectable with age owing to age-related somatic mosaicism, rather than oxidative damage.

broad.io

biorxiv.org

Mitochondrial NADH-redox inflexibility constrains genomic and epigenetic stability in pluripotent stem cells - The EMBO Journal

The electron transport chain (ETC) is essential for NAD+ regeneration and proliferation. While many cell types tolerate ETC inhibition when pyruvate or aspartate is supplied, pluripotent stem cells (P...

link.springer.com

Universal transcriptomic hallmarks of mammalian ageing and mortality - Nature

Integration of gene expression data from multiple tissues across four mammalian species reveals conserved transcriptomic signatures of mammalian ageing and mortality and uncovers the modular...

nature.com

Mitochondrial complex I activity promotes antigen cross-presentation in dendritic cells

Mitochondrial complex I dysfunction in dendritic cells disrupts NAD+/NADH redox balance and impairs antigen cross-presentation.

science.org

HCMV infection depends on EGLN1-mediated mitochondrial activation to increase dNTP pools for viral DNA replication

Simpson et al. report that HCMV utilizes EGLN1 to upregulate mitochondrial metabolism to support viral replication. EGLN1 is required for viral induction of dNTP synthesis to support viral DNA replica...

cell.com

Genetic analysis of circulating metabolic traits in 619,372 individuals - Nature

A genome-wide association study combining data from the Estonian Biobank and the UK Biobank identifies many common and low-frequency locus–metabolic trait associations, enabling the identification of ...

nature.com

Mitochondrial l-2-hydroxyglutarate is a physiological signalling metabolite - Nature

l-2-Hydroxyglutarate is identified as a legitimate physiological signalling metabolite, and control of its levels is essential for postnatal growth and survival and correct renal development and funct...

nature.com

Cardiolipin preserves Treg metabolic fitness and immune homeostasis in the gut - Nature Metabolism

This study describes that cardiolipin deficiency-induced mitochondrial dysfunction in Treg cells impairs gut–immune tolerance.

nature.com

Blue Power Ranger Billy: Okay, Now That's Cool!

ALT: Blue Power Ranger Billy: Okay, Now That's Cool!

static.klipy.com

Enrichment of Rare mtDNA Variants Among Individuals with Kidney Disease Reveals Undiagnosed Mitochondrial Disease

Pathogenic mitochondrial DNA (mtDNA) variants cause multisystem disease, yet their contribution to kidney disease remains incompletely characterized, …

sciencedirect.com

Yale-led technology receives FDA approval for breast cancer treatment

The biotech company Arvinas was originally founded based on pioneering research from Yale chemist Craig Crews into PROTAC protein degraders.

news.yale.edu

Succinate calls a time-out on pyrimidine biosynthesis - Nature Metabolism

Cell metabolism is a dynamic network of highly interconnected biochemical reactions. In this issue of Nature Metabolism, time-lapse analysis of the amino acid aspartate revealed an unexpected regulati...

nature.com

Succinate dehydrogenase loss suppresses pyrimidine biosynthesis via succinate-mediated inhibition of aspartate transcarbamylase - Nature Metabolism

Succinate acts as a competitive inhibitor of mammalian aspartate transcarbamylase (ATCase), leading to impaired pyrimidine biosynthesis and reduced proliferation under SDH inhibition.

nature.com