Mitochondrial enzymes are protected from stress-induced aggregation by mitochondrial chaperones and the Pim1/LON protease

Bender, Tom; Lewrenz, Ilka; Franken, Sebastian; Baitzel, Catherina; Voos, Wolfgang

doi:10.1091/mbc.e10-08-0718

Cited by 139 publications

(125 citation statements)

References 52 publications

(89 reference statements)

Supporting

Mentioning

120

Contrasting

Unclassified

Order By: Relevance

“…The up-regulation of HSP70 and HSP60 chaperones on transcript and protein levels in ftsh4 is consistent with their protective roles against the aggregation of mitochondrial proteins under oxidative stress conditions (Table I; Fig. 4A; Bender et al, 2011).…”

Section: Diverse Mitochondrial Proteins Undergo Carbonylation In Ftshsupporting

confidence: 77%

Lack of FTSH4 Protease Affects Protein Carbonylation, Mitochondrial Morphology, and Phospholipid Content in Mitochondria of Arabidopsis: New Insights into a Complex Interplay

et al. 2016

View full text Add to dashboard Cite

FTSH4 is one of the inner membrane-embedded ATP-dependent metalloproteases in mitochondria of Arabidopsis (Arabidopsis thaliana). In mutants impaired to express FTSH4, carbonylated proteins accumulated and leaf morphology was altered when grown under a short-day photoperiod, at 22°C, and a long-day photoperiod, at 30°C. To provide better insight into the function of FTSH4, we compared the mitochondrial proteomes and oxyproteomes of two ftsh4 mutants and wild-type plants grown under conditions inducing the phenotypic alterations. Numerous proteins from various submitochondrial compartments were observed to be carbonylated in the ftsh4 mutants, indicating a widespread oxidative stress. One of the reasons for the accumulation of carbonylated proteins in ftsh4 was the limited ATP-dependent proteolytic capacity of ftsh4 mitochondria, arising from insufficient ATP amount, probably as a result of an impaired oxidative phosphorylation (OXPHOS), especially complex V. In ftsh4, we further observed giant, spherical mitochondria coexisting among normal ones. Both effects, the increased number of abnormal mitochondria and the decreased stability/activity of the OXPHOS complexes, were probably caused by the lower amount of the mitochondrial membrane phospholipid cardiolipin. We postulate that the reduced cardiolipin content in ftsh4 mitochondria leads to perturbations within the OXPHOS complexes, generating more reactive oxygen species and less ATP, and to the deregulation of mitochondrial dynamics, causing in consequence the accumulation of oxidative damage.

show abstract

Section: Diverse Mitochondrial Proteins Undergo Carbonylation In Ftshsupporting

confidence: 77%

Lack of FTSH4 Protease Affects Protein Carbonylation, Mitochondrial Morphology, and Phospholipid Content in Mitochondria of Arabidopsis: New Insights into a Complex Interplay

et al. 2016

View full text Add to dashboard Cite

show abstract

“…Hsp60 forms the chaperonin complex, which is implicated in protein folding and assembly within the mitochondria under normal conditions [53]. Hsp60 together with its cochaperonin Hsp10 produce a large, efficient protein-editing machinery that facilitates proper folding and assembly of mitochondrial-imported proteins and corrects misfolded polypeptides generated under mitochondrial oxidative stress [57]. Mutations in the HSPD1 gene encoding Hsp60 have recently been found to underlie spastic paraplegia 13 (SPG13 [MIM 605280]), an autosomal-dominant spinal-cord neurodegenerative disorder of late onset, characterized by progressive weakness and spasticity of the lower limbs, and, more recently, a homozygous missense mutation, D29G, in HSPD1, encoding the mitochondrial Hsp60 chaperonin, causing a mitochondrial Hsp60 chaperonopathy linked to brain hypomyelination and leukodystrophy.…”

Section: Discussionmentioning

confidence: 99%

Redox regulation of cellular stress response in multiple sclerosis

Pennisi

Cornelius

Cavallaro

et al. 2011

Biochemical Pharmacology

View full text Add to dashboard Cite

Multiple sclerosis (MS) is an autoimmune-mediated neurodegenerative disease with characteristic foci of inflammatory demyelination in the brain, spinal cord, and optic nerves. Recent studies have demonstrated not only that axonal damage and neuronal loss are significant pathologic components of MS, but that this neuronal damage is thought to cause the permanent neurologic disability often seen in MS patients. Emerging finding suggests that altered redox homeostasis and increased oxidative stress, primarily implicated in the pathogenesis of MS, are a trigger for activation of a brain stress response. Relevant to maintenance of redox homeostasis, integrated mechanisms controlled by vitagenes operate in brain in preserving neuronal survival during stressful conditions. Vitagenes encode for heat shock proteins (Hsp) Hsp32, Hsp70, the thioredoxin and the sirtuin protein systems. In the present study we assess stress response mechanisms in the CSF, plasma and lymphocytes of control patients compared to MS patients. We found that the levels of vitagenes Hsp72, Hsc70, HO-1, as well as oxidative stress markers carbonyls and hydroxynonenals were significantly higher in the blood and CSF of MS patients than in control patients. In addition, an increased expression of Trx and sirtuin 1, together with a decrease in the expression of TrxR were observed. Our data strongly support a pivotal role for redox homeostasis disruption in the pathogenesis of MS and, consistently with the notion that new therapies that prevent neurodegeneration through nonimmunomodulatory mechanisms can have a tremendous potential to work synergistically with current MS therapies, unravel important targets for new cytoprotective strategies

show abstract

“…Although Lon can degrade mildly oxidized hydrophobic substrates, severely oxidized substrates aggregate, rendering them resistant to degradation . Lon functions in collaboration with the chaperone system, which keeps client proteins in an unfolded state until their proteolytic removal can be initiated (Wagner et al 1994;Bender et al 2011). The reduced level of unfoldase activity in Lon restricts its ability to degrade proteins that are folded and functional in the mitochondrial matrix (Koodathingal et al 2009).…”

Section: Atp-dependent Proteolysis In the Mitochondrial Matrixmentioning

confidence: 99%

Quality Control of Mitochondrial Proteostasis

Baker

Tatsuta²,

Langer

2011

Cold Spring Harbor Perspectives in Biology

225

193

View full text Add to dashboard Cite

A decline in mitochondrial activity has been associated with aging and is a hallmark of many neurological diseases. Surveillance mechanisms acting at the molecular, organellar, and cellular level monitor mitochondrial integrity and ensure the maintenance of mitochondrial proteostasis. Here we will review the central role of mitochondrial chaperones and proteases, the cytosolic ubiquitin-proteasome system, and the mitochondrial unfolded response in this interconnected quality control network, highlighting the dual function of some proteases in protein quality control within the organelle and for the regulation of mitochondrial fusion and mitophagy.

show abstract

Mitochondrial enzymes are protected from stress-induced aggregation by mitochondrial chaperones and the Pim1/LON protease

Cited by 139 publications

References 52 publications

Lack of FTSH4 Protease Affects Protein Carbonylation, Mitochondrial Morphology, and Phospholipid Content in Mitochondria of Arabidopsis: New Insights into a Complex Interplay

Lack of FTSH4 Protease Affects Protein Carbonylation, Mitochondrial Morphology, and Phospholipid Content in Mitochondria of Arabidopsis: New Insights into a Complex Interplay

Redox regulation of cellular stress response in multiple sclerosis

Quality Control of Mitochondrial Proteostasis

Contact Info

Product

Resources

About