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Complex I mitochondria briefs

5 importance briefs tagged Complex I, including the current week and the archive.

• biorxiv2026-10-28score 92

  NDUFA13 lysine-7 acetylation is the switch from OXPHOS failure to cristae collapse in heart failure

  Nan, Yang, Liu, He and colleagues identify acetylation of the Complex I accessory subunit NDUFA13 at lysine 7 as the sensor that turns OXPHOS inhibition into cristae disintegration. Hyperacetylated NDUFA13 compacts, moves toward the intermembrane space, binds PHB2, displaces PHB1, and takes apart prohibitin scaffolds. The acetylation mimic K7Q fragments cristae in cells. Cardiomyocyte-specific K7Q knock-in mice die faster under pressure overload, lose cristae, slow the TCA cycle and fatty acid oxidation, and selectively deplete polyunsaturated cardiolipins. NDUFA13 is not an Fe-S subunit. Complex I's N-module carries Fe-S clusters; this abstract does not name them or a couple at K7. The chemistry on the residue is lysine acetylation, reversed in principle by deacetylation. The membrane chemistry that fails downstream is polyunsaturated cardiolipin.

• biorxiv2026-07-27score 92

  Diabetic human kidney cortex respires faster as tissue while its isolated mitochondria, and Complex I, are already weaker

  Granata, Coughlan and colleagues profiled fresh kidney cortex from living people with diabetes and still-preserved kidney function. Permeabilized tissue shows higher respiratory flux. Mitochondria isolated from the same cortex show lower respiratory capacity and impaired Complex I activity. Tubular cells carry more mitochondrial volume and a more fragmented network. The early lesion is not a uniform shutdown. It is weaker organelles, including Complex I, covered by a larger, remodeled mitochondrial pool. Complex I's iron-sulfur chain is the enzyme behind the activity loss, and the abstract does not name the cluster.

• biorxiv2026-08-04score 91

  Cholesterol in APOE4 astrocytes truncates cristae, drops Complexes I and IV, and leaves cells dependent on a reversing ATP synthase

  Lee, Holt and colleagues find that APOE4 mouse astrocytes with high intracellular cholesterol build sparse, truncated cristae and extra crista-junction complexes, lose respiratory Complexes I and IV, and respire less. Membrane potential still rises, because proton leak is low and ATP synthase runs in reverse, hydrolyzing ATP to support the gradient. Oligomycin becomes selectively toxic, and sequestering cholesterol with methyl-β-cyclodextrin removes that toxicity. The lost complexes imply iron-sulfur, heme, and copper sites. The abstract reports the complexes, not the metals. The enzyme they actually catch misbehaving is ATP synthase.

• biorxiv2026-07-29score 86

  Ringer loss weakens fruit-fly Complex I, raises superoxide, and matches a Complex I deficit in Parkinson disease brain

  Tillmon and colleagues place Ringer, the Drosophila homolog of human tubulin polymerization promoting protein (TPPP), in the mitochondrial matrix and show that losing it lowers Complex I subunits, assembly factors, and enzymatic activity. The oxygen species they measure is superoxide. Complex I moves electrons from NADH through FMN into a chain of iron-sulfur clusters and out to ubiquinone at cluster N2, but this abstract never names which cluster or which core oxidation level failed. The Parkinson link is real as a claim and thin as a dataset: they say postmortem human brain shows similar deficits, without listing the human subunits.

• biorxiv2026-08-04score 80

  Black carbon holds immune cells in an OMA1-DELE1 stress response; ultrafine particles and nanoplastics take shorter paths

  In human peripheral blood mononuclear cells, ultrafine particulate matter, black carbon, and polystyrene nanoplastics all move oxidative stress and mitochondrial markers, but not on the same clock. Ultrafine particles look acute and adaptive. Black carbon looks chronic, with a persistent OMA1-DELE1 integrated stress response and inflammation. Polystyrene nanoplastics sit in between: lower, longer adaptation plus biogenesis. ND1 and Complexes I through V are expression markers here, not measured iron-sulfur or copper centers. OMA1's metal is also unnamed.

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