Evidence map›Paper›PMID 42715104›Full record

ArticleCell reports2026

Mitochondrial Fis1 tunes Rab7A activity via TBC1D15 modulating STING degradation.

Eunice Dominguez-Martin, Linlin Lei, Jennifer D Petersen, Peng-Peng Zhu, Katherine R Tucker, Richard J Youle

Abstract read
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In one paragraph

Article in Cell reports, 2026. 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
–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

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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

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

6 authors.

Eunice Dominguez-MartinSurgical Neurology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health (NINDS), Bethesda, MD 20892, USA. Electronic address: eunice.dominguezmartin@jefferson.edu.
Linlin LeiSurgical Neurology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health (NINDS), Bethesda, MD 20892, USA.
Jennifer D PetersenSurgical Neurology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health (NINDS), Bethesda, MD 20892, USA; Electron Microscopy Core Facility, National Institute of Neurological Disorders and Stroke, National Institutes of Health (NINDS), Bethesda, MD 20892, USA.
Peng-Peng ZhuSurgical Neurology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health (NINDS), Bethesda, MD 20892, USA.
Katherine R TuckerSurgical Neurology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health (NINDS), Bethesda, MD 20892, USA.
Richard J YouleSurgical Neurology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health (NINDS), Bethesda, MD 20892, USA. Electronic address: youler@ninds.nih.gov.

Funding

Role of mitochondria in neurodegenerative diseasesZIANS003123 · NINDS · NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE · PI YOULE, RICHARD JAMES · 2011 to 2025
$28.8M
Mechanisms of AutophagyZIANS003127 · NINDS · NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE · PI YOULE, RICHARD JAMES · 2011 to 2025
$16.7M
Intramural NIH HHS ZIA NS003123Intramural NIH HHS ZIA NS003127
6 · The paper itself

Abstract

The mechanisms governing the final trafficking steps of the cyclic dinucleotide innate immune receptor stimulator of interferon genes (STING) are not fully understood. Here, we identify the mitochondrial protein Fis1 as a regulator of STING endolysosomal degradation. The absence of Fis1 in HeLa cells stabilizes STING, boosting downstream signaling without affecting its initial endoplasmic reticulum (ER)-to-Golgi traffic. Instead, Fis1 loss impairs STING delivery to endolysosomes. Fis1 recruits the Rab7A-GAP TBC1D15 to mitochondria and upon STING activation, TBC1D15 localization shifts to the Golgi. In the absence of Fis1, the interaction between TBC1D15 and Rab7A is disrupted, leading to decreased Rab7A GTPase activity and impaired STING degradation. Our findings reveal a mitochondria-controlled axis where Fis1 tunes Rab7A activity via TBC1D15, which is required to ensure proper STING degradation, directly linking mitochondria to lysosomal trafficking and the termination of innate immune signaling.

Indexed as

GTPase-Activating ProteinsMembrane ProteinsMitochondriaMitochondrial Proteinsrab GTP-Binding ProteinscGAS-STING Signaling PathwayEndoplasmic ReticulumEndosomesGolgi ApparatusHeLa CellsHumansLysosomesProtein TransportProteolysisrab7 GTP-Binding ProteinsSTING ProteinGTPase-Activating ProteinsMembrane ProteinsMitochondrial Proteinsrab7 GTP-Binding Proteinsrab7 GTP-binding proteins, humanrab GTP-Binding ProteinsSTING1 protein, humanSTING ProteinTBC1D15 protein, humanCP: cell biologyCP: immunologyFis1Golgiinnate immunitylysosomal degradationmitochondriaRab7Rab-GAPSTINGTBC1D15traffic

Identifiers

PMID42715104
PMCPMC13667912

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Registered trials

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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.