Rare diseases affect millions of people worldwide, yet they remain understudied. Six experts on rare metabolic diseases reflect on the state of the field and share their perspectives on the opportunit...

The citric acid cycle (TCA cycle) is the common terminal pathway for the oxidation of all nutrients. Citrate oxidation to oxaloacetate produces CO2, and citrate synthase (CS) uses nutrient-derived ace...

Researchers are racing to culture a menagerie of exotic organisms and finding lots of surprises along the way.

NADPH derived from the pentose phosphate pathway is shown to mediate exercise-induced physiological cardiac hypertrophy and protect against damage caused by ischaemia–reperfusion injury.

Khan et al. show that long-term nicotinamide riboside produces divergent tissue responses in mitochondrial progeria mice: it restores cardiac NAD+ metabolism and function, but in bone marrow causes re...

Mitochondrial DNA (mtDNA) encodes core subunits of the oxidative phosphorylation machinery, and its expression is spatially organized, with the genome packaged into nucleoids around which transcriptio...

Injection of a person’s own mitochondria into the retina was safe but had only a temporary effect on restoring vision.

Mild mitochondrial stress could extend lifespan across species, yet the underlying mechanism remains unclear. Here, we show that inhibition of mitochondrial respiration induces a sustained transcripti...

Probabilistic sequence encoding from language model embeddings within a generative AI framework enables protein miniaturization, modification and augmentation while maintaining native architectur...

The cellular distribution of mitochondria in response to stress and local energy needs is governed by the relative activities of the microtubule-based molecular motors kinesin and dynein. The mechanis...

Mitochondrial dysfunction features prominently in tauopathies. The mechanistic link between tau and mitochondria remains uncertain. Li et al. show that tau enters mitochondria and interacts with compl...

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...

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...

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

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...

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...

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

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.

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...

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...

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

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...

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 ...

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...

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

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

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

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

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...

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

Metformin is shown to exert its glucose-lowering and additional clinical effects through inhibition of mitochondrial complex I in the intestinal epithelium in mice.