PXD054844

PXD054844 is an original dataset announced via ProteomeXchange.

Title	LETMD1 regulates mitochondrial protein synthesis and import to guard brown fat mitochondrial integrity and function
Description	Thermogenic brown and beige adipocytes (BA) are powerful agents against the growing global obesity epidemic, as they break down lipids to generate heat. We and others have recently shown that LETM1-domain containing 1 (LETMD1) is a cold-induced protein essential for mitochondrial cristae structure and thermogenic function of BA. Still, how LETMD1 regulates thermogenesis of BA remains unclear. Here we first demonstrated that LETMD1 is a mitochondrial inner membrane protein. We next generated a BA-specific UCP1-Cre mediated Letmd1 knockout (Letmd1UKO) mouse model to show that LETMD1 plays a cell autonomous role in maintaining the structure and function of BA. We further uncovered robust mitochondrial autophagy (mitophagy) and protein aggregation within Letmd1UKO BA, in conjunction with elevated levels of reactive oxidative stress and mitochondrial hyperpolarization. We then used TurboID proximity labeling to identify candidate LETMD1-interacting proteins, many of which are associated with the mitochondrial protein import machinery and electron transport chain Complexes I and IV. We finally used quantitative proteomics to reveal an enrichment of Complex I and IV proteins within the insoluble protein aggregates. These results suggest that LETMD1 facilitates the mitochondrial import of respiratory chain proteins to maintain BA cristae structure and thermogenesis.
HostingRepository	jPOST
AnnounceDate	2024-08-14
AnnouncementXML	Submission_2024-08-13_17:07:02.511.xml
DigitalObjectIdentifier
ReviewLevel	Non peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Yi-Kai Liu
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	S-carboxamidomethyl-L-cysteine; alpha-amino acetylated residue; L-methionine sulfoxide
Instrument	instrument; Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2024-08-13 17:06:58	ID requested
⏵ 1	2024-08-13 17:07:02	announced

Dataset with its publication pending

submitter keyword: Thermogenesis, Brown adipocytes, Adipose tissue, LETM1, TIM complex, electron transport chain, mitochondrial respiration

Shihuan Kuang, W. Andy Tao
lab head
Yi-Kai Liu
contact affiliation	Purdue University
dataset submitter

jPOST dataset URI

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