PXD021867

PXD021867 is an original dataset announced via ProteomeXchange.

Title	Proteomics profiling of Lrpprc knockout mice liver mitochondria following resolution by hybrid CN/BN PAGE
Description	Mouse models of genetic mitochondrial diseases are generally used to understand specific molecular defects and their biochemical consequences, but rarely to map compensatory changes allowing survival. Here we took advantage of the extraordinary mitochondrial resilience of hepatic Lrpprc knockout mice to explore this question using native proteomics profiling and lipidomics. In these mice, lack of the mtRNA binding protein LRPPRC induces a global mitochondrial translation defect and a severe reduction (>80%) in the assembly and activity of the electron transport chain (ETC) complex IV (CIV). Yet, animals show no signs of liver failure and capacity of the ETC is completely preserved. Beyond stimulation of mitochondrial biogenesis, results show that the abundance of mitoribosomes per unit of mitochondria is increased and proteostatic mechanisms are induced in absence of LRPPRC to preserve a balance in the availability of mitochondrial- vs nuclear-encoded ETC subunits. At the level of individual organelles, a strong preferential integration of residual CIV in supercomplexes (SCs) is observed, pointing to a role of these supramolecular arrangements in preserving ETC function. This can be mechanistically explained by the upregulation of the assembly factor COX7A2L and its stabilization into SCs. Furthermore, lipidomics and proteomics evidences indicate a shift in the phospholipids composition of mitochondrial membrane including an upregulation of SC stabilizing cardiolipin (CL) species, and several CL-binding protein complexes playing key roles in CL metabolism. Together these data reveal a complex in vivo network of molecular adjustments involved in preserving mitochondrial integrity in energy consuming organs facing OXPHOS defects, which could be therapeutically exploited.
HostingRepository	PRIDE
AnnounceDate	2021-09-09
AnnouncementXML	Submission_2021-09-09_07:47:38.208.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Goutham Vasam
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2020-10-06 23:08:46	ID requested
⏵ 1	2021-09-09 07:47:38	announced

Cuillerier A, Ruiz M, Daneault C, Forest A, Rossi J, Vasam G, Cairns G, Cadete V, Des Rosiers C, Burelle Y, Aliskashani A, Allen BG, Aubut C, Bemeur C, Beauchamp C, Burelle Y, Charron G, Coderre L, Des Rosiers C, Desch, ê, nes S, Labarthe F, Landry J, Laprise C, Lavall, é, e G, Lavoie P, Maranda B, Morin C, Mukaneza Y, Nishimura T, Rioux JD, Rivard M È, Sasarman F, Shoubridge EA, Tardif J, Legault JT, Tremblay N, Tremblay-Vaillancourt V, Vachon L, Villeneuve J, Adaptive optimization of the OXPHOS assembly line partially compensates lrpprc-dependent mitochondrial translation defects in mice. Commun Biol, 4(1):989(2021) [pubmed]

submitter keyword: Genetic mitochondrial disease, Lrpprc, liver mitochondria, mitochondrial supercomplexes, mitochondrial translation, mitochondrial electron transport chain, mitochondrial biogenesis, mitochondrial proteostasis, mitoribosomes, mitochondrial lipidomics, mitochondrial proteomics, cardiolipin, mitochondrial membrane lipids

Yan Burelle
contact affiliation	Professor, University Research Chair in Integrative Mitochondrial Biology, Interdisciplinary School of Health Sciences, Faculty of Health Sciences, University of Ottawa, Canada
contact email	yburell2@uottawa.ca
lab head
Goutham Vasam
contact affiliation	Postdoctoral Fellow
contact email	gvasam@uottawa.ca
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD021867
     1. Label: PRIDE project
     2. Name: Proteomics profiling of Lrpprc knockout mice liver mitochondria following resolution by hybrid CN/BN PAGE