Acanthamoeba ATP synthase structure reveals the TCA cycle is tethered to OXPHOS

Original title: Acanthamoeba ATP synthase structure reveals the TCA cycle is tethered to OXPHOS.

Oxidative phosphorylation (OXPHOS) is a key metabolic process that couples redox energy to ATP production.

By Fry, Luce, Stefely +8CellOct 1, 2026

Score█████░░░░░4.6

VerdictCompetent work. Briefs at most.

Read the original

Abstract

Oxidative phosphorylation (OXPHOS) is a key metabolic process that couples redox energy to ATP production. While some core OXPHOS complex subunits are found across all domains of life, many have diverged or expanded across evolution-as seen in the protozoan pathogen Acanthamoeba castellanii. By integrating cryo-electron microscopy of unenriched mitochondrial lysate with mass spectrometry proteomics, we resolved the structures of endogenous mitochondrial ATP synthase (complex V), Hsp60, and respiratory complex III from Acanthamoeba. We capture Acanthamoeba ATP synthase in an IF1-inhibited state and reveal how Acanthamoeba-specific subunits and extensions stabilize the molecular machine, which includes a β subunit extension that interfaces with the peripheral stalk. Additionally, we characterize an active malate dehydrogenase (MDH) dimer structurally integrated within the ATP synthase peripheral stalk, thus revealing a direct protein tether between OXPHOS and the tricarboxylic acid cycle. Together, these findings provide structural insight into lineage-specific adaptations in Acanthamoeba that may tune protozoan metabolism.

Michelle Y Fry, Bridget E Luce, Jonathan A Stefely, Michael Z Chen, Felicia G Deng, Tiana M Issa, MitoCarta Tree of Life Consortium, Sarah E Calvo, John Samuelson, Vamsi K Mootha, Luke H Chao

The editor's rubric

Heuristic review

Dimension	Level	Weight	What that level means
Leverage	██░░░ 2	24%	Reusable within one subfield (a technique, dataset, or protocol a few groups will adopt).
Magnitude	██░░░ 2	16%	Solid incremental gain on a meaningful problem.
Evidence	███░░ 3	20%	Solid: multiple benchmarks or cohorts, ablations, fair baselines, released code or data.
Novelty	██░░░ 2	20%	A new combination of known ideas.
Trajectory	██░░░ 2	10%	Some room to improve with obvious engineering.
Stakes	██░░░ 2	10%	Benefits a professional community (practitioners, clinicians, engineers).

Editor’s rationale

Heuristic triage from title and abstract text only, not a reading of the paper. Cues found: verification (experimental validation).

How the score was computed

rank-2026-09-29

Score█████░░░░░4.6

Score = 10 × (75% × adjusted merit / 10 + 15% × attention + 10% × freshness)

Merit: 4.4 / 10; Weighted rubric, evidence-gated.
Adjusted merit: 4.1 / 10; Shrunk toward the desk prior by editor confidence (32%).
Attention: 46%; Citations, upvotes, points, mentions.
Freshness: 80%; Half-life decay since publication.

Citations3 (reference 20, via openalex, Oct 3, 2026, 05:48 UTC)
Field-weighted citation impact13.5 (reference 3, via openalex, Oct 3, 2026, 05:48 UTC)

The record

Reviewed by heuristic-v2 on Oct 3, 2026, 05:48 UTC. Paper type: empirical.
Categories: Journal Article, Mitochondria, Acanthamoeba castellanii, Mitochondrial Proton-Translocating ATPases, Malate Dehydrogenase, Protozoan Proteins, Cryoelectron Microscopy, Citric Acid Cycle, Oxidative Phosphorylation, Models, Molecular
TOP, No.6 in the Biology edition of October 3, 2026.