Mitochondrial proteome of Acanthamoeba delineates aerobic and anaerobic pathways dynamically regulated by oxygen

Original title: Mitochondrial proteome of Acanthamoeba delineates aerobic and anaerobic pathways dynamically regulated by oxygen.

Acanthamoeba castellanii causes infectious blindness and resides in a key evolutionary outgroup to humans and fungi.

By Stefely, Deng, Chen +17CellOct 1, 2026

Score█████░░░░░4.6

VerdictCompetent work. Briefs at most.

Read the original

Abstract

Acanthamoeba castellanii causes infectious blindness and resides in a key evolutionary outgroup to humans and fungi. Its divergent mitochondria are of outstanding interest due to their predicted aerobic and anaerobic functions with potential for drug targeting. However, a detailed delineation of its bioenergetic machinery, its activities, and their regulation remains lacking. Here, we integrate mitochondrial immunoprecipitation, density gradient purification, mass spectrometry, protein correlation profiling, and microscopy to generate a high-confidence inventory of the Acanthamoeba mitoproteome. The resulting AcMitoCarta contains 1,122 proteins, including 381 lacking readily identifiable homologs in human and yeast mitochondria. Complexome analysis highlights 20 macromolecular assemblies. Complementary proteomic and transcriptomic profiling reveals extensive rewiring of the organelle's bioenergetic machinery by oxygen, including induction of an anaerobic pyruvate:ferredoxin oxidoreductase-to-hydrogenase pathway under anoxia. We experimentally demonstrate that Acanthamoeba can produce H2 gas under anoxic conditions via a mitochondria-localized, oxygen-labile hydrogenase. AcMitoCarta establishes a framework for dissecting the interplay between aerobic and anaerobic energy metabolism.

Jonathan A Stefely, Felicia G Deng, Michael Z Chen, Khanh Nguyen, Bridget E Luce, Michelle Y Fry, Xiaoyan A Guo, Konstantinos Maliaris, Keith D Rivera, Malvina Papanastasiou, Tiana M Issa, Bharath Kanakapura Sundararaj, Sophia L Y Root, D R Mani, MitoCarta Tree of Life Consortium, Luke H Chao, Sarah E Calvo, Namrata D Udeshi, John Samuelson, Vamsi K Mootha

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. No strong cues found.

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 (30%).
Attention: 49%; Citations, upvotes, points, mentions.
Freshness: 80%; Half-life decay since publication.

Citations4 (reference 20, via openalex, Oct 3, 2026, 05:48 UTC)
Field-weighted citation impact17.9 (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, Humans, Acanthamoeba castellanii, Oxygen, Mitochondrial Proteins, Proteome, Protozoan Proteins, Proteomics, Aerobiosis
TOP, No.3 in the Biology edition of October 3, 2026.