Difference between revisions of "Rawat 2019 J Mol Biol"
(Created page with "{{Publication |title=Rawat S, Anusha V, Jha M, Sreedurgalakshmi K, Raychaudhuri S (2019) Aggregation of respiratory complex subunits marks the onset of proteotoxicity in prote...") Β |
Β |
||
(One intermediate revision by one other user not shown) | |||
Line 1: | Line 1: | ||
{{Publication | {{Publication | ||
|title=Rawat S, Anusha V, Jha M, Sreedurgalakshmi K, Raychaudhuri S (2019) Aggregation of respiratory complex subunits marks the onset of proteotoxicity in proteasome inhibited cells. J Mol Biol | |title=Rawat S, Anusha V, Jha M, Sreedurgalakshmi K, Raychaudhuri S (2019) Aggregation of respiratory complex subunits marks the onset of proteotoxicity in proteasome inhibited cells. J Mol Biol 431:996-1015. | ||
|info=[https://www.ncbi.nlm.nih.gov/pubmed/30682348 PMID: 30682348 Open Access] | |info=[https://www.ncbi.nlm.nih.gov/pubmed/30682348 PMID: 30682348 Open Access] | ||
|authors=Rawat S, Anusha V, Jha M, Sreedurgalakshmi K, Raychaudhuri S | |authors=Rawat S, Anusha V, Jha M, Sreedurgalakshmi K, Raychaudhuri S | ||
Line 8: | Line 8: | ||
<small>Copyright Β© 2019. Published by Elsevier Ltd.</small> | <small>Copyright Β© 2019. Published by Elsevier Ltd.</small> | ||
|keywords=Low complexity region, Mitochondria, Mitochondrial respiratory chain complex, Protein aggregation, Protein misfolding, Protein turnover, Proteomics, Proteostasis | |keywords=Low complexity region, Mitochondria, Mitochondrial respiratory chain complex, Protein aggregation, Protein misfolding, Protein turnover, Proteomics, Proteostasis, Neuro2a mouse neuroblastoma cells | ||
|editor=[[Plangger M]], | |editor=[[Plangger M]], | ||
|mipnetlab=IN Hyderabad Thangaraj K | |mipnetlab=IN Hyderabad Thangaraj K | ||
Line 15: | Line 15: | ||
|area=Respiration | |area=Respiration | ||
|organism=Mouse | |organism=Mouse | ||
|tissues=Nervous system | |tissues=Nervous system, Other cell lines | ||
|preparations=Permeabilized cells | |preparations=Permeabilized cells | ||
|couplingstates=OXPHOS | |couplingstates=LEAK, OXPHOS | ||
|pathways=N, S, CIV, ROX | |pathways=N, S, CIV, ROX | ||
|instruments=Oxygraph-2k | |instruments=Oxygraph-2k | ||
|additional= | |additional=2019-01, | ||
}} | }} |
Latest revision as of 11:11, 14 August 2019
Rawat S, Anusha V, Jha M, Sreedurgalakshmi K, Raychaudhuri S (2019) Aggregation of respiratory complex subunits marks the onset of proteotoxicity in proteasome inhibited cells. J Mol Biol 431:996-1015. |
Rawat S, Anusha V, Jha M, Sreedurgalakshmi K, Raychaudhuri S (2019) J Mol Biol
Abstract: Proteostasis is maintained by optimal expression, folding, transport, and clearance of proteins. Deregulation of any of these processes triggers protein aggregation and is implicated in many age-related pathologies. In this study, 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 the cleavable mitochondrial targeting sequence (MTS), contain low complexity regions (LCR) at the N-terminus. Using different chimeric and mutant constructs, we show that these low complexity regions partially contribute to the 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 eventually deregulates the biogenesis of respiratory complexes and marks the onset of mitochondrial dysfunction.
Copyright Β© 2019. Published by Elsevier Ltd. β’ Keywords: Low complexity region, Mitochondria, Mitochondrial respiratory chain complex, Protein aggregation, Protein misfolding, Protein turnover, Proteomics, Proteostasis, Neuro2a mouse neuroblastoma cells β’ Bioblast editor: Plangger M β’ O2k-Network Lab: IN Hyderabad Thangaraj K
Labels: MiParea: Respiration
Organism: Mouse
Tissue;cell: Nervous system, Other cell lines
Preparation: Permeabilized cells
Coupling state: LEAK, OXPHOS
Pathway: N, S, CIV, ROX
HRR: Oxygraph-2k
2019-01