Han et al. use biochemistry and acute depletion of senataxin to reveal a role in RNAPII transcript elongation via reversal of pausing and backtracking. By contrast, senataxin has little direct effect on transcription termination.

Nature Structural & Molecular Biology, Published online: 10 November 2025; doi:10.1038/s41594-025-01710-6He, Teng and Yang et al. report how metformin, the widely used antidiabetic drug, inhibit its target, the respiratory complex I, through a distinct state-dependent, inhibitor trapping mechanism, thus providing the molecular basis for its superior clinical tolerance.

Protein–lipid interactions play a crucial role in the stability and function of membrane proteins. While experimental approaches to characterize these interactions in a native-like membrane environmen...

Chhikara et al. reframe stromal interaction molecule (STIM) proteins as structural organizers of membrane contact sites, not just calcium-entry activators, in neurons. STIM2 maintains resting endoplasmic reticulum (ER)–plasma membrane (PM) junctions; STIM1 dynamically expands them during neuronal activity. This activity-dependent remodeling tunes ER–PM proximity and calcium coupling, shifting focus from channel gating to spatial organization.

BRD4 functions as an intracellular pH sensor through a conserved histidine-rich intrinsically disordered region. Inflammation-associated acidification triggers a pH-dependent switch in transcriptional...

Abrams et al. used circular permutation to develop a reversible FRET-based cysteine sensor. Biochemical and cell-based experiments established the sensor’s sensitivity and selectivity for cysteine. High-throughput phenotypic screens identified compounds that modulate cysteine levels, establishing the sensor as a valuable tool for studying cellular cysteine regulation.

Bridge-like lipid transfer proteins (BLTPs) play central roles in redistributing lipids from their primary site of synthesis in the endoplasmic reticulum to other organelles. They comprise bridge-doma...

This study reveals how cardiolipin governs mitochondrial morphology by modulating the activity of human OPA1 and how its replacement by monolyso-cardiolipin, as observed in Barth syndrome, impacts…

Acetyl-coenzyme A functions as a non-canonical signal to trigger mitophagy, and the acetyl-coenzyme A–NLRX1 axis underlies the KRAS-inhibitor-induced mitophagy response and promotes drug resistan...

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Senataxin (SETX) regulates RNA polymerase II (RNAPII) transcription and helps maintain genome stability, at least partly by suppressing R-loops. Howev…

Acetyl-coenzyme A functions as a non-canonical signal to trigger mitophagy, and the acetyl-coenzyme A–NLRX1 axis underlies the KRAS-inhibitor-induced mitophagy response and promotes drug resistan...