PXD040502-2

PXD040502 is an original dataset announced via ProteomeXchange.

Title	Mitochondrial mechanotransduction through MIEF1 coordinates the nuclear response to forces
Description	Tissue-scale architecture and mechanical properties instruct cell behavior in physiological and diseased conditions, but our understanding of the underlying mechanisms remains fragmentary. Here we show that ECM stiffness, spatial confinements, and applied forces including stretching of the mouse skin regulate mitochondrial dynamics. Actomyosin tension promotes phosphorylation of MIEF1, limiting the recruitment of DRP1 at mitochondria, peri-mitochondrial F-actin formation, and mitochondrial fission. Strikingly, mitochondrial fission is also a general mechanotransduction mechanism. Indeed we found that DRP1- and MIEF1-dependent fission is required and sufficient to regulate three transcription factors of broad relevance such as YAP-TAZ, SREBP1-2, and NRF2 to control cell proliferation, lipogenesis, antioxidant metabolism, chemotherapy resistance, and adipocyte differentiation in response to mechanical cues. This extends to the mouse liver, where DRP1 regulates hepatocyte proliferation and identity, hallmark YAP-dependent phenotypes. We propose that mitochondria fulfill a unifying signaling function by which the mechanical tissue microenvironment coordinates complementary cell functions.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_06:57:37.883.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Sirio Dupont
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	phosphorylated residue
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2023-02-28 08:41:38	ID requested
1	2024-09-02 05:21:02	announced
⏵ 2	2024-10-22 06:57:38	announced	2024-10-22: Updated project metadata.

Dataset with its publication pending

submitter keyword: TAZ,mitochondria, YAP, DRP1, MIEF1

Sirio Dupont
contact affiliation	Department of Molecular Medicine, University of Padova, Italy
contact email	sirio.dupont@unipd.it
lab head
Sirio Dupont
contact affiliation	Department of Molecular Medicine
contact email	sirio.dupont@unipd.it
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD040502
     1. Label: PRIDE project
     2. Name: Mitochondrial mechanotransduction through MIEF1 coordinates the nuclear response to forces