RGD Reference Report - Transmission of cell stress from endoplasmic reticulum to mitochondria: enhanced expression of Lon protease. - Rat Genome Database

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Transmission of cell stress from endoplasmic reticulum to mitochondria: enhanced expression of Lon protease.

Authors: Hori, O  Ichinoda, F  Tamatani, T  Yamaguchi, A  Sato, N  Ozawa, K  Kitao, Y  Miyazaki, M  Harding, HP  Ron, D  Tohyama, M  M Stern, D  Ogawa, S 
Citation: Hori O, etal., J Cell Biol 2002 Jun 24;157(7):1151-60.
RGD ID: 633879
Pubmed: PMID:12082077   (View Abstract at PubMed)
PMCID: PMC2173558   (View Article at PubMed Central)
DOI: DOI:10.1083/jcb.200108103   (Journal Full-text)

The rat homologue of a mitochondrial ATP-dependent protease Lon was cloned from cultured astrocytes exposed to hypoxia. Expression of Lon was enhanced in vitro by hypoxia or ER stress, and in vivo by brain ischemia. These observations suggested that changes in nuclear gene expression (Lon) triggered by ER stress had the potential to impact important mitochondrial processes such as assembly and/or degradation of cytochrome c oxidase (COX). In fact, steady-state levels of nuclear-encoded COX IV and V were reduced, and mitochondrial-encoded subunit II was rapidly degraded under ER stress. Treatment of cells with cycloheximide caused a similar imbalance in the accumulation of COX subunits, and enhanced mRNA for Lon and Yme1, the latter another mitochondrial ATP-dependent protease. Furthermore, induction of Lon or GRP75/mtHSP70 by ER stress was inhibited in PERK (-/-) cells. Transfection studies revealed that overexpression of wild-type or proteolytically inactive Lon promoted assembly of COX II into a COX I-containing complex, and partially prevented mitochondrial dysfunction caused by brefeldin A or hypoxia. These observations demonstrated that suppression of protein synthesis due to ER stress has a complex effect on the synthesis of mitochondrial-associated proteins, both COX subunits and ATP-dependent proteases and/or chaperones contributing to assembly of the COX complex.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
LONP1Humanbrain ischemia  ISOLonp1 (Rattus norvegicus) RGD 
Lonp1Ratbrain ischemia  IDA  RGD 
Lonp1Mousebrain ischemia  ISOLonp1 (Rattus norvegicus) RGD 
Lonp1Ratischemia  IDA  RGD 

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Lonp1Ratprotein-containing complex assembly  IMP  RGD 
Lonp1Ratresponse to hypoxia  IEP  RGD 

Objects Annotated

Genes (Rattus norvegicus)
Lonp1  (lon peptidase 1, mitochondrial)

Genes (Mus musculus)
Lonp1  (lon peptidase 1, mitochondrial)

Genes (Homo sapiens)
LONP1  (lon peptidase 1, mitochondrial)


Additional Information