Evidence map›Paper›PMID 41672147›Full record

ArticleMolecular & cellular proteomics : MCP2026

Subcellular Proteomic Analyses Reveal REEP5 Knockdown in the Mouse Heart Disrupts Mitochondrial Networks.

Michelle Di Paola, Cristine J Reitz, Uros Kuzmanov, Kateleen Jia, Anthony O Gramolini

Abstract read
In one paragraph

Article in Molecular & cellular proteomics : MCP, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. Review
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

5 authors.

Michelle Di PaolaTranslational Biology and Engineering Program, Ted Rogers Centre for Heart Research, Toronto, Ontario, Canada; Department of Physiology, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada.
Cristine J ReitzTranslational Biology and Engineering Program, Ted Rogers Centre for Heart Research, Toronto, Ontario, Canada; Department of Physiology, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada.
Uros KuzmanovTranslational Biology and Engineering Program, Ted Rogers Centre for Heart Research, Toronto, Ontario, Canada; Department of Physiology, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada.
Kateleen JiaTranslational Biology and Engineering Program, Ted Rogers Centre for Heart Research, Toronto, Ontario, Canada; Department of Physiology, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada.
Anthony O GramoliniTranslational Biology and Engineering Program, Ted Rogers Centre for Heart Research, Toronto, Ontario, Canada; Department of Physiology, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada. Electronic address: anthony.gramolini@utoronto.ca.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Receptor Expression-Enhancing Protein 5 (REEP5) is a cardiac-enriched, membrane-shaping protein localized to the sarco(endo)plasmic reticulum (SR/ER), where it supports membrane network architecture and cardiomyocyte function. While REEP5 has been implicated in calcium handling and contractility, its role in regulating inter-organelle communication and mitochondrial homeostasis remains less well-understood. In this study, we used recombinant adeno-associated virus serotype 9-mediated shRNA knockdown of Reep5 in mouse hearts, combined with subcellular fractionation and data-independent acquisition mass spectrometry, to define proteomic remodeling across microsomal (SR/ER), mitochondrial, and cytosolic compartments. Loss of REEP5 altered the composition of SR/ER membrane-shaping proteins, including upregulation of RTN4, ATL3, and CKAP4, suggesting a partial compensatory response. Microsomal, mitochondrial and cytosolic proteomes exhibited broad reorganization, with enrichment of proteins involved in redox adaptation and proteostasis, alongside depletion of mitochondrial import machinery and antioxidant enzymes. Imaging of isolated cardiomyocytes confirmed fragmented mitochondrial networks and increased reactive oxygen species, consistent with proteomic signatures of disrupted mitochondrial dynamics and oxidative stress. Gene ontology enrichment across all fractions highlighted widespread dysregulation in organelle-specific processes, including translation, protein localization, and metabolic remodeling. Notably, several altered pathways converged on mitochondria-associated membranes, suggesting that REEP5 may support SR/ER-mitochondria tethering and functional crosstalk. These findings position REEP5 as a key regulator of organelle homeostasis in the heart and underscore how its loss disrupts mitochondrial integrity and inter-organelle communication across cellular compartments.

Indexed as

Membrane ProteinsMitochondriaMitochondria, HeartMyocardiumProteomicsAnimalsCytosolEndoplasmic ReticulumGene Knockdown TechniquesMiceMice, Inbred C57BLMyocytes, CardiacOxidative StressProteomeReactive Oxygen SpeciesSarcoplasmic ReticulumMembrane ProteinsProteomeReactive Oxygen SpeciesDIA LC-MS/MSmitochondriaoxidative stressREEP5SR/ER

Identifiers

PMID41672147
PMCPMC13014923

What Socratic holds

Textmetadata
LicenceCC BY
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.