Evidence map›Paper›PMID 38746426›Full record

ArticlebioRxiv : the preprint server for biology2025

Ancestral sequence reconstruction of the Mic60 Mitofilin domain reveals residues supporting respiration in yeast.

Friederike M C Benning, Tristan A Bell, Tran H Nguyen, Della Syau, Louise B Connell, Yi-Ting Liao, Matthew P Keating, Margaret Coughlin, Anja E H Nordstrom, Maria Ericsson and 2 more

Abstract readPreprint
In one paragraph

Article in bioRxiv : the preprint server for biology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
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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

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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

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

12 authors.

Friederike M C BenningDepartment of Molecular Biology, Massachusetts General Hospital, Boston, MA 02114, USA.ORCID 0000-0002-1002-4204
Tristan A BellDepartment of Molecular Biology, Massachusetts General Hospital, Boston, MA 02114, USA.ORCID 0000-0002-3668-8412
Tran H NguyenDepartment of Molecular Biology, Massachusetts General Hospital, Boston, MA 02114, USA.ORCID 0009-0007-6084-3017
Della SyauDepartment of Molecular Biology, Massachusetts General Hospital, Boston, MA 02114, USA.ORCID 0000-0002-8192-2220
Louise B ConnellDepartment of Chemistry and Biomolecular Sciences, University of Ottawa, Ottawa, Ontario K1N 6N5, Canada.ORCID 0000-0002-3276-8626
Yi-Ting LiaoDepartment of Molecular Biology, Massachusetts General Hospital, Boston, MA 02114, USA.ORCID 0000-0001-5050-7481
Matthew P KeatingDepartment of Biology, Boston University, Boston, MA 02215, USA.
Margaret CoughlinElectron Microscopy Core Facility, Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA.
Anja E H NordstromElectron Microscopy Core Facility, Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA.
Maria EricssonElectron Microscopy Core Facility, Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA.ORCID 0000-0002-4563-3683
Corrie J B daCostaDepartment of Chemistry and Biomolecular Sciences, University of Ottawa, Ottawa, Ontario K1N 6N5, Canada.ORCID 0000-0002-9546-5331
Luke H ChaoDepartment of Molecular Biology, Massachusetts General Hospital, Boston, MA 02114, USA.ORCID 0000-0002-4849-4148

Funding

Probing structural and biophysical mechanisms of mitochondrial membrane ultrastructureR35GM142553 · NIGMS · MASSACHUSETTS GENERAL HOSPITAL · PI Luke H. Chao · 2021 to 2026
$2.6M
NIGMS NIH HHS R35 GM142553
6 · The paper itself

Abstract

In eukaryotes, cellular respiration takes place in the cristae of mitochondria. The mitochondrial inner membrane protein Mic60, a core component of the mitochondrial contact site and cristae organizing system (MICOS), is crucial for the organization and stabilization of crista junctions and its associated functions. While the C-terminal Mitofilin domain of Mic60 is necessary for cellular respiration, the sequence determinants for this function have remained unclear. Here, we used ancestral sequence reconstruction to generate Mitofilin ancestors up to and including the last opisthokont common ancestor (LOCA). We found that yeast-lineage derived Mitofilin ancestors as far back as the LOCA rescue respiration. By comparing Mitofilin ancestors, we identified four residues sufficient to explain the respiratory difference between yeast- and animal-derived Mitofilin ancestors. Our results provide a foundation for investigating the conservation of Mic60-mediated cristae junction interactions.

Identifiers

PMID38746426
PMCPMC11092495

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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.