Evidence map›Paper›PMID 40016208›Full record

ArticleNature communications2025

Kingdom-specific lipid unsaturation calibrates sequence evolution in membrane arm subunits of eukaryotic respiratory complexes.

Pooja Gupta, Sristi Chakroborty, Arun K Rathod, K Ranjith Kumar, Shreya Bhat, Suparna Ghosh, Pallavi Rao T, Kameshwari Yele, Raman Bakthisaran, R Nagaraj and 2 more

Abstract read
In one paragraph

Article in Nature communications, 2025. 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
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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

12 authors.

Pooja GuptaCSIR- Centre for Cellular and Molecular Biology, Uppal Road, Hyderabad - 500007, India.ORCID http://orcid.org/0009-0009-9488-3716
Sristi ChakrobortyCSIR- Centre for Cellular and Molecular Biology, Uppal Road, Hyderabad - 500007, India.ORCID http://orcid.org/0009-0008-6345-3353
Arun K RathodAcademy of Scientific and Innovative Research (AcSIR), Ghaziabad - 201002, India.ORCID http://orcid.org/0000-0003-3424-2705
K Ranjith KumarCSIR- Centre for Cellular and Molecular Biology, Uppal Road, Hyderabad - 500007, India.
Shreya BhatCSIR- Centre for Cellular and Molecular Biology, Uppal Road, Hyderabad - 500007, India.
Suparna GhoshCSIR- Centre for Cellular and Molecular Biology, Uppal Road, Hyderabad - 500007, India.
Pallavi Rao TCSIR- Centre for Cellular and Molecular Biology, Uppal Road, Hyderabad - 500007, India.
Kameshwari YeleCSIR- Centre for Cellular and Molecular Biology, Uppal Road, Hyderabad - 500007, India.
Raman BakthisaranCSIR- Centre for Cellular and Molecular Biology, Uppal Road, Hyderabad - 500007, India.
R NagarajCSIR- Centre for Cellular and Molecular Biology, Uppal Road, Hyderabad - 500007, India.
Moutusi MannaAcademy of Scientific and Innovative Research (AcSIR), Ghaziabad - 201002, India.ORCID http://orcid.org/0000-0001-9472-1594
Swasti RaychaudhuriCSIR- Centre for Cellular and Molecular Biology, Uppal Road, Hyderabad - 500007, India. rcswasti@ccmb.res.in.ORCID http://orcid.org/0000-0003-4091-7991

Funding

Council of Scientific and Industrial Research (CSIR) HCP47Council of Scientific and Industrial Research (CSIR) MLP0143Council of Scientific and Industrial Research (CSIR) MLP0159
6 · The paper itself

Abstract

Sequence evolution of protein complexes (PCs) is constrained by protein-protein interactions (PPIs). PPI-interfaces are predominantly conserved and hotspots for disease-related mutations. How do lipid-protein interactions (LPIs) constrain sequence evolution of membrane-PCs? We explore Respiratory Complexes (RCs) as a case study as these allow to compare sequence evolution in subunits exposed to both lipids in inner-mitochondrial membrane (IMM) and lipid-free aqueous matrix. We find that lipid-exposed surfaces of the IMM-subunits but not of the matrix subunits are populated with non-PPI disease-causing mutations signifying LPIs in stabilizing RCs. Further, IMM-subunits including their exposed surfaces show high intra-kingdom sequence conservation but remarkably diverge beyond. Molecular Dynamics simulation suggests contrasting LPIs of structurally superimposable but sequence-wise diverged IMM-exposed helices of Complex I (CI) subunit Ndufa1 from human and Arabidopsis depending on kingdom-specific unsaturation of cardiolipin fatty acyl chains. in cellulo assays consolidate inter-kingdom incompatibility of Ndufa1-helices due to the lipid-exposed amino acids. Plant-specific unsaturated fatty acids in human cells also trigger CI-instability. Taken together, we posit that altered LPIs calibrate sequence evolution at the IMM-arms of eukaryotic RCs.

Indexed as

Electron Transport Complex IEvolution, MolecularLipidsMitochondrial MembranesAmino Acid SequenceArabidopsisCardiolipinsHumansMolecular Dynamics SimulationMutationProtein SubunitsCardiolipinsElectron Transport Complex ILipidsProtein Subunits

Identifiers

PMID40016208
PMCPMC11868549

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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 OpenQuestion graph.