Evidence map›Paper›PMID 37276406›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2023

A molecular rotor FLIM probe reveals dynamic coupling between mitochondrial inner membrane fluidity and cellular respiration.

Gaurav Singh, Geen George, Sufi O Raja, Ponnuvel Kandaswamy, Manoj Kumar, Shashi Thutupalli, Sunil Laxman, Akash Gulyani

Open access · greenAbstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.

0numbers the graph read from it
0cells of the map it votes in
17citing papers in PubMed
4.8field-weighted citation impact, top 4% 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

17 citing papers in PubMed, 31 citations in OpenAlex.

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  9. Active control of mitochondrial network morphology by metabolism-driven redox state.Proceedings of the National Academy of Sciences of the United States of America · 2025
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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

8 authors at 3 institutions in 1 country.

Gaurav SinghInstitute for Stem Cell Science and Regenerative Medicine, 560065 Bangalore, India.ORCID 0000-0001-8514-0739
Geen GeorgeInstitute for Stem Cell Science and Regenerative Medicine, 560065 Bangalore, India.
Sufi O RajaDepartment of Biochemistry, School of Life Sciences, University of Hyderabad, 500046 Hyderabad, India.ORCID 0000-0001-5355-1453
Ponnuvel KandaswamyInstitute for Stem Cell Science and Regenerative Medicine, 560065 Bangalore, India.
Manoj KumarSimons Centre for the Study of Living Machines, National Centre for Biological Sciences, Tata Institute of Fundamental Research, 560065 Bangalore, India.ORCID 0000-0001-6999-6764
Shashi ThutupalliSimons Centre for the Study of Living Machines, National Centre for Biological Sciences, Tata Institute of Fundamental Research, 560065 Bangalore, India.ORCID 0000-0002-4728-937X
Sunil LaxmanInstitute for Stem Cell Science and Regenerative Medicine, 560065 Bangalore, India.ORCID 0000-0002-0861-5080
Akash GulyaniInstitute for Stem Cell Science and Regenerative Medicine, 560065 Bangalore, India.ORCID 0000-0003-4130-4257
Institute for Stem Cell Biology and Regenerative Medicine · INTata Institute of Fundamental Research · INUniversity of Hyderabad · IN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The inner mitochondrial membrane (IMM), housing components of the electron transport chain (ETC), is the site for respiration. The ETC relies on mobile carriers; therefore, it has long been argued that the fluidity of the densely packed IMM can potentially influence ETC flux and cell physiology. However, it is unclear if cells temporally modulate IMM fluidity upon metabolic or other stimulation. Using a photostable, red-shifted, cell-permeable molecular-rotor, Mitorotor-1, we present a multiplexed approach for quantitatively mapping IMM fluidity in living cells. This reveals IMM fluidity to be linked to cellular-respiration and responsive to stimuli. Multiple approaches combining in vitro experiments and live-cell fluorescence (FLIM) lifetime imaging microscopy (FLIM) show Mitorotor-1 to robustly report IMM 'microviscosity'/fluidity through changes in molecular free volume. Interestingly, external osmotic stimuli cause controlled swelling/compaction of mitochondria, thereby revealing a graded Mitorotor-1 response to IMM microviscosity. Lateral diffusion measurements of IMM correlate with microviscosity reported via Mitorotor-1 FLIM-lifetime, showing convergence of independent approaches for measuring IMM local-order. Mitorotor-1 FLIM reveals mitochondrial heterogeneity in IMM fluidity; between-and-within cells and across single mitochondrion. Multiplexed FLIM lifetime imaging of Mitorotor-1 and NADH autofluorescence reveals that IMM fluidity positively correlates with respiration, across individual cells. Remarkably, we find that stimulating respiration, through nutrient deprivation or chemically, also leads to increase in IMM fluidity. These data suggest that modulating IMM fluidity supports enhanced respiratory flux. Our study presents a robust method for measuring IMM fluidity and suggests a dynamic regulatory paradigm of modulating IMM local order on changing metabolic demand.

Indexed as

Mitochondrial MembranesCell RespirationDiffusionMembrane FluidityMolecular ProbesOsmotic PressureMolecular Probesfluidityfluorescence lifetimefluorescent probemetabolismmitochondria

Identifiers

PMID37276406
PMCPMC10268597
OpenAlexW4379468948

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.