Evidence map›Paper›PMID 31730859›Full record

ArticleCell2019

A Compendium of Genetic Modifiers of Mitochondrial Dysfunction Reveals Intra-organelle Buffering.

Tsz-Leung To, Alejandro M Cuadros, Hardik Shah, Wendy H W Hung, Yang Li, Sharon H Kim, Daniel H F Rubin, Ryan H Boe, Sneha Rath, John K Eaton and 8 more

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

Article in Cell, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 94 papers.

0numbers the graph read from it
0cells of the map it votes in
94citing papers in PubMed
6.3field-weighted citation impact, top 3% 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

94 citing papers in PubMed, 153 citations in OpenAlex.

  1. Article
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  19. Formation of ICell metabolism · 2025
    Article
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34 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

18 authors at 3 institutions in 1 country.

Tsz-Leung ToBroad Institute of Harvard and MIT, Cambridge, MA 02142, USA.
Alejandro M CuadrosBroad Institute of Harvard and MIT, Cambridge, MA 02142, USA.
Hardik ShahBroad Institute of Harvard and MIT, Cambridge, MA 02142, USA; Howard Hughes Medical Institute, Massachusetts General Hospital, Boston, MA 02114, USA, Massachusetts General Hospital, Boston, MA 02114, USA; Department of Molecular Biology, Massachusetts General Hospital, Boston, MA 02114, USA.
Wendy H W HungBroad Institute of Harvard and MIT, Cambridge, MA 02142, USA.
Yang LiBroad Institute of Harvard and MIT, Cambridge, MA 02142, USA; Howard Hughes Medical Institute, Massachusetts General Hospital, Boston, MA 02114, USA, Massachusetts General Hospital, Boston, MA 02114, USA; Department of Molecular Biology, Massachusetts General Hospital, Boston, MA 02114, USA.
Sharon H KimBroad Institute of Harvard and MIT, Cambridge, MA 02142, USA; Howard Hughes Medical Institute, Massachusetts General Hospital, Boston, MA 02114, USA, Massachusetts General Hospital, Boston, MA 02114, USA; Department of Molecular Biology, Massachusetts General Hospital, Boston, MA 02114, USA.
Daniel H F RubinBroad Institute of Harvard and MIT, Cambridge, MA 02142, USA; Howard Hughes Medical Institute, Massachusetts General Hospital, Boston, MA 02114, USA, Massachusetts General Hospital, Boston, MA 02114, USA; Department of Molecular Biology, Massachusetts General Hospital, Boston, MA 02114, USA.
Ryan H BoeBroad Institute of Harvard and MIT, Cambridge, MA 02142, USA.
Sneha RathBroad Institute of Harvard and MIT, Cambridge, MA 02142, USA; Howard Hughes Medical Institute, Massachusetts General Hospital, Boston, MA 02114, USA, Massachusetts General Hospital, Boston, MA 02114, USA; Department of Molecular Biology, Massachusetts General Hospital, Boston, MA 02114, USA.
John K EatonBroad Institute of Harvard and MIT, Cambridge, MA 02142, USA.
Federica PiccioniBroad Institute of Harvard and MIT, Cambridge, MA 02142, USA.
Amy GoodaleBroad Institute of Harvard and MIT, Cambridge, MA 02142, USA.
Zohra KalaniBroad Institute of Harvard and MIT, Cambridge, MA 02142, USA.
John G DoenchBroad Institute of Harvard and MIT, Cambridge, MA 02142, USA.
David E RootBroad Institute of Harvard and MIT, Cambridge, MA 02142, USA.
Stuart L SchreiberBroad Institute of Harvard and MIT, Cambridge, MA 02142, USA; Howard Hughes Medical Institute, Massachusetts General Hospital, Boston, MA 02114, USA, Massachusetts General Hospital, Boston, MA 02114, USA; Department of Chemistry and Chemical Biology, Harvard University, Cambridge, MA 02138, USA.
Scott B VafaiBroad Institute of Harvard and MIT, Cambridge, MA 02142, USA.
Vamsi K MoothaBroad Institute of Harvard and MIT, Cambridge, MA 02142, USA; Howard Hughes Medical Institute, Massachusetts General Hospital, Boston, MA 02114, USA, Massachusetts General Hospital, Boston, MA 02114, USA; Department of Molecular Biology, Massachusetts General Hospital, Boston, MA 02114, USA. Electronic address: vamsi@hms.harvard.edu.
Broad Institute · USHoward Hughes Medical Institute · USMassachusetts General Hospital · US

Funding

Medical Scientist Training ProgramT32GM007753 · NIGMS · HARVARD UNIVERSITY (MEDICAL SCHOOL) · PI WALENSKY, LOREN DAVID · 1985 to 2021
$50.0M
Mitochondrial Parts, Pathways, and PathogenesisR35GM122455 · NIGMS · BROAD INSTITUTE, INC. · PI MOOTHA, VAMSI KRISHNA · 2017 to 2021
$4.0M
Molecular Determinants of Mitochondrial Genome Abundance and IntegrityK00CA212468 · NCI · MASSACHUSETTS GENERAL HOSPITAL · PI RATH, SNEHA PRAKASH · 2019 to 2022
$385k
Howard Hughes Medical InstituteNCI NIH HHS K00 CA212468NIGMS NIH HHS R35 GM122455NIGMS NIH HHS T32 GM007753
6 · The paper itself

Abstract

Mitochondrial dysfunction is associated with a spectrum of human conditions, ranging from rare, inborn errors of metabolism to the aging process. To identify pathways that modify mitochondrial dysfunction, we performed genome-wide CRISPR screens in the presence of small-molecule mitochondrial inhibitors. We report a compendium of chemical-genetic interactions involving 191 distinct genetic modifiers, including 38 that are synthetic sick/lethal and 63 that are suppressors. Genes involved in glycolysis (PFKP), pentose phosphate pathway (G6PD), and defense against lipid peroxidation (GPX4) scored high as synthetic sick/lethal. A surprisingly large fraction of suppressors are pathway intrinsic and encode mitochondrial proteins. A striking example of such "intra-organelle" buffering is the alleviation of a chemical defect in complex V by simultaneous inhibition of complex I, which benefits cells by rebalancing redox cofactors, increasing reductive carboxylation, and promoting glycolysis. Perhaps paradoxically, certain forms of mitochondrial dysfunction may best be buffered with "second site" inhibitors to the organelle.

Indexed as

Genes, ModifierAutoantigensCell DeathCytosolElectron Transport Complex IEpistasis, GeneticFerroptosisGenomeGlutathione PeroxidaseGlycolysisHumansK562 CellsMitochondriaOligomycinsOxidation-ReductionOxidative PhosphorylationAutoantigensElectron Transport Complex IGlutathione PeroxidaseOligomycinsReactive Oxygen SpeciesRibonucleoproteinsSS-B Antigencomplex ICRISPR screeningG6PDgenetic modifierGPX4LARP1metforminmitochondriaredox cofactorsreductive carboxylation

Identifiers

PMID31730859
PMCPMC7053407
OpenAlexW2985065511

What OpenQuestion holds

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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.