PXD012204

PXD012204 is an original dataset announced via ProteomeXchange.

Title	Aggregation of respiratory complex subunits marks the onset of proteotoxicity in proteasome inhibited cells
Description	Proteostasis is maintained by optimum expression, folding, transport, and clearance of proteins. Deregulation of any of these processes triggers protein aggregation and is implicated in many age-related pathologies. Here, using quantitative proteomics and microscopy we show that aggregation of many nuclear-encoded mitochondrial proteins is an early protein-destabilization event during short-term proteasome inhibition. Among these, Respiratory Chain Complex (RCC) subunits represent a group of functionally related proteins consistently forming aggregates under multiple proteostasis-stresses with varying aggregation-propensities. Sequence analysis reveals that several RCC subunits, irrespective of cleavable mitochondrial targeting sequence (MTS), contain low complexity regions (LCR) at N-terminus. Using different chimeric and mutant constructs we show that these low complexity regions partially contribute to intrinsic instability of multiple RCC subunits. Taken together, we propose that physicochemically driven aggregation of unassembled RCC subunits destabilizes their functional assembly inside mitochondria. This deregulates the biogenesis of respiratory complexes and marks the onset of mitochondrial dysfunction.
HostingRepository	PRIDE
AnnounceDate	2019-01-28
AnnouncementXML	Submission_2019-01-28_05:05:32.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Swasti Raychaudhuri
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	No PTMs are included in the dataset
Instrument	LTQ Orbitrap Velos; Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2018-12-31 03:23:27	ID requested
⏵ 1	2019-01-28 05:05:33	announced

Rawat S, Anusha V, Jha M, Sreedurgalakshmi K, Raychaudhuri S, Aggregation of Respiratory Complex Subunits Marks the Onset of Proteotoxicity in Proteasome Inhibited Cells. J Mol Biol, 431(5):996-1015(2019) [pubmed]

submitter keyword: Proteostasis, protein aggregation, protein misfolding, protein turnover, proteomics, low complexity region, mitochondria, mitochondrial respiratory chain complex

Swasti Raychaudhuri
contact affiliation	CSIR-Centre for Cellular and Molecular Biology, Uppal Road, Hyderabad - 500007, India
contact email	rcswasti@ccmb.res.in
lab head
Swasti Raychaudhuri
contact affiliation	CSIR-Centre for Cellular and Molecular Biology
contact email	rcswasti@ccmb.res.in
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD012204
     1. Label: PRIDE project
     2. Name: Aggregation of respiratory complex subunits marks the onset of proteotoxicity in proteasome inhibited cells