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biorxiv2026-10-28Complex Icristaeprohibitincardiolipin

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.

Mito.news · at a glance

Signal profile (abstract-level)

Complex I · cristae · prohibitin · cardiolipin

Score 85/100BIORXIVmedium confidenceComplex I
85
Importance
70
Mito signal
95
Dysfunction
75
Evidence
73
Translational

Editorial signal profile from the abstract (importance score, mito keywords, dysfunction tags, evidence density, translational cues). Not a figure reproduced from the preprint PDF.

Verdict. When OXPHOS stalls, NDUFA13 is acetylated at K7, leaves its post, and dismantles prohibitin cristae scaffolds. Heart-failure inner membranes fail as a PTM, not only as a missing respiratory polypeptide.

Metal sites and redox

Complex I (NADH:ubiquinone oxidoreductase) carries FMN and eight iron-sulfur clusters in the N- and Q-modules. NDUFA13 (GRIM-19) is an accessory subunit on the transmembrane arm, not one of those Fe-S proteins. This abstract does not name a cluster, a core oxidation level, or NAD+/NADH as the K7 chemistry. The modification is lysine acetylation. Downstream membrane chemistry is loss of polyunsaturated cardiolipins, which can in other literature peroxidize, but the authors do not report lipid ROS. Do not invent [4Fe-4S] involvement at K7. If OXPHOS inhibition is the input, the Fe-S enzymes are upstream of the sensor, not the measured site.

What the authors report

OXPHOS inhibition acetylates NDUFA13-K7. The subunit compacts and heads toward the intermembrane space. It binds PHB2's coiled-coil, kicks off PHB1, and the prohibitin ring comes apart. K7Q is enough to break cristae in culture. In cardiomyocytes in the mouse, K7Q plus pressure overload accelerates death, erases cristae, slows TCA and fat oxidation, and removes PUFA-cardiolipins. They call it reversible and want targeted deacetylation.

What was measured

K7 acetylation after OXPHOS block, conformation and localization, PHB2/PHB1 biochemistry, K7Q morphology, knock-in survival and ultrastructure, TCA flux, FAO, cardiolipin species.

Caveats

No named KAT or sirtuin. K7Q is not acetyl-lysine. Cardiolipin loss mechanism unspecified. Abstract is short; dose of OXPHOS inhibitors is not given.

What to do with it

Treat cristae collapse in failing heart as an NDUFA13-K7 acetylation problem sitting on prohibitins and PUFA-cardiolipin. The molecular test is whether blocking that acetylation, or restoring PHB1/PHB2, keeps cristae when the chain is inhibited.

Bibliographic record

FieldValue
TitleAcetylation of NDUFA13 at K7 Senses OXPHOS Dysfunction to Disrupt Prohibitin Scaffolds and Drive Cristae Remodelling in Heart Failure
DOI10.64898/2026.10.26.761921
Serverbiorxiv
Posted2026-10-28
TopicsComplex I, cristae, prohibitin, cardiolipin, heart failure, acetylation
Mitos score85/100
Confidencemedium
HTMLhttps://www.biorxiv.org/content/10.64898/2026.10.26.761921
PDFhttps://www.biorxiv.org/content/10.64898/2026.10.26.761921.full.pdf

Abstract-based editorial synthesis by Mitos. Not peer review.

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Source preprint

Acetylation of NDUFA13 at K7 Senses OXPHOS Dysfunction to Disrupt Prohibitin Scaffolds and Drive Cristae Remodelling in Heart Failure

10.64898/2026.10.26.761921

Nan J, Yang X, Lin Y, Shen J, Chen H, Xu Z, Ye J, Wang Y, Xiong D, Ke C, Zhu L, Kong X, Zhong Z, Ren T, Jiang J, Wang X, Wang B, Zhao D, Li Z, Shao Z, Liu B, He X.

Open on biorxiv →PDF