Evidence map›Paper›PMID 37596294›Full record

ArticleNature communications2023

Mitochondria are secreted in extracellular vesicles when lysosomal function is impaired.

Wenjing Liang, Shakti Sagar, Rishith Ravindran, Rita H Najor, Justin M Quiles, Liguo Chi, Rachel Y Diao, Benjamin P Woodall, Leonardo J Leon, Erika Zumaya and 5 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature communications, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 171 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
171citing papers in PubMed, 1 pooled it
34.0field-weighted citation impact, top 1% of its field
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

171 citing papers in PubMed, 1 synthesis or guideline pooled it, 212 citations in OpenAlex.

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  15. Extracellular vesicles and epigenetic aging clocks in tissue aging: an exosome-focused conceptual framework with a focus on skin.The journals of gerontology. Series A, Biological sciences and medical sciences · 2026
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111 more citing papers are in PubMed but not listed here.

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

15 authors at 1 institution in 1 country.

Wenjing LiangSkaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, La Jolla, CA, USA.
Shakti SagarSkaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, La Jolla, CA, USA.
Rishith RavindranSkaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, La Jolla, CA, USA.
Rita H NajorSkaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, La Jolla, CA, USA.
Justin M QuilesSkaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, La Jolla, CA, USA.
Liguo ChiSkaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, La Jolla, CA, USA.
Rachel Y DiaoSkaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, La Jolla, CA, USA.
Benjamin P WoodallSkaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, La Jolla, CA, USA.
Leonardo J LeonSkaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, La Jolla, CA, USA.
Erika ZumayaSkaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, La Jolla, CA, USA.
Jason DuranDepartment of Medicine, University of California San Diego, La Jolla, CA, USA.
David M CauviDepartment of Surgery, University of California San Diego, La Jolla, CA, USA.
Antonio De MaioDepartment of Surgery, University of California San Diego, La Jolla, CA, USA.
Eric D AdlerDepartment of Medicine, University of California San Diego, La Jolla, CA, USA.
Åsa B GustafssonSkaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, La Jolla, CA, USA. abgustafsson@ucsd.edu.ORCID http://orcid.org/0000-0001-6347-8210
University of California San Diego · US

Funding

U of Calif, San Diego Neuroscience Microscopy ImagingP30NS047101 · NINDS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI GLEESON, JOSEPH G, ZHENG, BINHAI · 2003 to 2022
$9.0M
Secretion of mitochondria as a cellular quality control mechanismR01HL155281 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI GUSTAFSSON, ASA B. · 2021 to 2024
$2.3M
Autophagy and Megamitochondria in Cardiac Aging and Heart FailureR01HL157265 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI GUSTAFSSON, ASA B. · 2021 to 2024
$1.9M
JEOL JEM-1400Plus Transmission Electron MicroscopeS10OD023527 · OD · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI FARQUHAR, MARILYN GIST · 2017 to 2017
$579k
NHLBI NIH HHS R01 HL155281NHLBI NIH HHS R01 HL157265NIH HHS S10 OD023527NINDS NIH HHS P30 NS047101
6 · The paper itself

Abstract

Mitochondrial quality control is critical for cardiac homeostasis as these organelles are responsible for generating most of the energy needed to sustain contraction. Dysfunctional mitochondria are normally degraded via intracellular degradation pathways that converge on the lysosome. Here, we identified an alternative mechanism to eliminate mitochondria when lysosomal function is compromised. We show that lysosomal inhibition leads to increased secretion of mitochondria in large extracellular vesicles (EVs). The EVs are produced in multivesicular bodies, and their release is independent of autophagy. Deletion of the small GTPase Rab7 in cells or adult mouse heart leads to increased secretion of EVs containing ubiquitinated cargos, including intact mitochondria. The secreted EVs are captured by macrophages without activating inflammation. Hearts from aged mice or Danon disease patients have increased levels of secreted EVs containing mitochondria indicating activation of vesicular release during cardiac pathophysiology. Overall, these findings establish that mitochondria are eliminated in large EVs through the endosomal pathway when lysosomal degradation is inhibited.

Indexed as

Extracellular VesiclesLysosomesAnimalsBiological TransportMiceMitochondriaMultivesicular Bodies

Identifiers

PMID37596294
PMCPMC10439183
OpenAlexW4385971551

What OpenQuestion holds

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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 OpenQuestion graph.