Evidence map›Paper›PMID 42822427›Full record

ArticleCell2026

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

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 and 1 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

2 citing papers in PubMed.

  1. Article
  2. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

11 authors.

Michelle Y FryDepartment of Molecular Biology, Massachusetts General Hospital, Boston, MA 02114, USA; Department of Genetics, Blavatnik Institute, Harvard Medical School, Boston, MA 02115, USA.
Bridget E LuceDepartment of Molecular Biology, Massachusetts General Hospital, Boston, MA 02114, USA; Department of Genetics, Blavatnik Institute, Harvard Medical School, Boston, MA 02115, USA.
Jonathan A StefelyDepartment of Molecular Biology, Massachusetts General Hospital, Boston, MA 02114, USA; Harvard Medical School, Boston, MA 02115, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Howard Hughes Medical Institute, Massachusetts General Hospital, Boston, MA 02114, USA; Department of Molecular and Cell Biology, Boston University Goldman School of Dental Medicine, Boston, MA 02118, USA.
Michael Z ChenDepartment of Molecular Biology, Massachusetts General Hospital, Boston, MA 02114, USA; Harvard Medical School, Boston, MA 02115, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Howard Hughes Medical Institute, Massachusetts General Hospital, Boston, MA 02114, USA.
Felicia G DengDepartment of Molecular Biology, Massachusetts General Hospital, Boston, MA 02114, USA; Harvard Medical School, Boston, MA 02115, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Howard Hughes Medical Institute, Massachusetts General Hospital, Boston, MA 02114, USA.
Tiana M IssaDepartment of Molecular Biology, Massachusetts General Hospital, Boston, MA 02114, USA; Harvard Medical School, Boston, MA 02115, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Howard Hughes Medical Institute, Massachusetts General Hospital, Boston, MA 02114, USA.
MitoCarta Tree of Life Consortium
Sarah E CalvoDepartment of Molecular Biology, Massachusetts General Hospital, Boston, MA 02114, USA; Harvard Medical School, Boston, MA 02115, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Howard Hughes Medical Institute, Massachusetts General Hospital, Boston, MA 02114, USA.
John SamuelsonDepartment of Molecular and Cell Biology, Boston University Goldman School of Dental Medicine, Boston, MA 02118, USA.
Vamsi K MoothaDepartment of Molecular Biology, Massachusetts General Hospital, Boston, MA 02114, USA; Harvard Medical School, Boston, MA 02115, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Howard Hughes Medical Institute, Massachusetts General Hospital, Boston, MA 02114, USA.
Luke H ChaoDepartment of Molecular Biology, Massachusetts General Hospital, Boston, MA 02114, USA; Department of Genetics, Blavatnik Institute, Harvard Medical School, Boston, MA 02115, USA. Electronic address: chao@molbio.mgh.harvard.edu.

Funding

Probing structural and biophysical mechanisms of mitochondrial membrane ultrastructureR35GM142553 · NIGMS · MASSACHUSETTS GENERAL HOSPITAL · PI Luke H. Chao · 2021 to 2026
$2.6M
Establishing Acanthamoeba as a modern model parasite for infectious disease biology and comparative metabolism by defining mitochondrial proteins and pathwaysK08AI193194 · NIAID · MORGRIDGE INSTITUTE FOR RESEARCH, INC. · PI Jonathan Allan Stefely · 2025 to 2026
$358k
Howard Hughes Medical InstituteNIAID NIH HHS K08 AI193194NIGMS NIH HHS R35 GM142553
6 · The paper itself

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.

Indexed as

Acanthamoeba castellaniiCitric Acid CycleMitochondrial Proton-Translocating ATPasesOxidative PhosphorylationCryoelectron MicroscopyMalate DehydrogenaseMitochondriaModels, MolecularProtozoan ProteinsMalate DehydrogenaseMitochondrial Proton-Translocating ATPasesProtozoan ProteinsAcanthamoebaATP synthasecomplex Vcryo-EMcrystallographymalate dehydrogenasemitochondriaoxidative phosphorylationrespiratory complexestricarboxylic acid cycle

Identifiers

PMID42822427
PMCPMC13632647

What Socratic holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.