The m-AAA Protease Defective in Hereditary Spastic Paraplegia Controls Ribosome Assembly in Mitochondria

Nolden, Mark; Ehses, Sarah; Koppen, Mirko; Bernacchia, Andrea; Rugarli, Elena I.; Langer, Thomas

doi:10.1016/j.cell.2005.08.003

Cited by 349 publications

(340 citation statements)

References 43 publications

(32 reference statements)

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“…Comparing Opa1 processing and mitochondrial morphology between Opa1 and Paraplegin deficient mice [100] will show which protein is the major processor for Opa1. Parapelgin, however, has also been implicated in the proper ribosome assembly in mitochondria [101] and reduction of paraplegin can also induce complex 1 deficiency and sensitivity to oxidative stress [102]. The effect of paraplegin on Opa1 processing, therefore, may not be direct, and could be through other proteins such as PARL.…”

Section: Mitochondrial Fusion Proteinsmentioning

confidence: 99%

Mitochondrial dynamics in the regulation of neuronal cell death

2007

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Mitochondria undergo continuous fission and fusion events in physiological situations. Fragmentation of mitochondria during cell death has been shown to play a key role in cell death progression, including release of the mitochondrial apoptotic proteins. Ultrastructural changes in mitochondria, such as cristae remodeling, is also involved in cell death initiation. Here, we emphasize the important role of mitochondrial fission/fusion machinery in neuronal cell death. Unlike many other cell types such as immortalized cell lines, neurons are distinct morphologically and functionally. We will discuss how this uniqueness presents special challenges in the cellular response to neurotoxic stresses, and how this affects the mitochondrial dynamics in the regulation of cell death in neurons.

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Section: Mitochondrial Fusion Proteinsmentioning

confidence: 99%

Mitochondrial dynamics in the regulation of neuronal cell death

2007

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“…Further, yeast strains defective in Yta10 or Yta12 are deficient in the proteolytic processing of the mitochondrial ribosomal protein MrpL32 ( Figure 1D; Nolden et al, 2005). Cells expressing Yta10-GFP or YTA12-GFP process MrpL32 as wild-type cells ( Figure 1D), demonstrating that the m-AAA protease exhibits normal proteolytic activity in these strains.…”

Section: Yta10-gfp and Yta12-gfp Complement The Untagged Proteinsmentioning

confidence: 99%

“…Because the respiration deficiency phenotype of ⌬yta10 cells is due to lack of mature MrpL32 (Nolden et al, 2005), we reasoned that the impaired maturation of MrpL32 might also determine the absence of cristae in the mitochondria of ⌬yta12 cells. To examine this possibility, we expressed mature MrpL32, targeted to the mitochondrial matrix by the residues 1-65 of subunit 9 of the F 1 F O -ATPase of Neurospora crassa in ⌬yta12 cells.…”

Section: Pccp1-gfp Is Preferentially Localized In the Ibmmentioning

confidence: 99%

“…For expression of the hybrid protein Su9(1-69)-MrpL32(72-183), the respective fragment of MRPL32 was amplified from yeast genomic DNA with the primers GCG CGC GGT ACC GCA GTT CCT AAA AAA AAA G and GCG CGC CTC GAG CTA GTC CTT TTT TAA AGT CC and cloned in the vector pVT100U-mtGFP (Westermann and Neupert, 2000) via KpnI/XhoI, replacing the coding sequence of green fluorescent protein (GFP) with that of MrpL32(72-183), as described (Nolden et al, 2005). A yeast strain expressing Ccp1-GFP and Qcr2-monomeric red fluorescent protein (mRFP) was first transformed with the resulting plasmid pVT100U-mtMrpL32(72-183) and then, in a second step, a targeted gene disruption of YTA12 was performed.…”

Section: Growth Media Strain Construction and Cloningmentioning

confidence: 99%

“…The m-AAA protease is a hetero-oligomeric complex composed of the homologous subunits AFG3L2 and paraplegin in humans (Atorino et al, 2003) and Yta10 (Afg3) and Yta12 (Rca1) in the budding yeast Saccharomyces cerevisiae (Arlt et al, 1996). Mutations in the m-AAA protease cause severe defects in various organisms, including respiratory deficiency in budding yeast (Arlt et al, 1998), accumulation of aberrant mitochondria in paraplegin-deficient mice (Ferreirinha et al, 2004) and neurodegeneration in humans (Nolden et al, 2005). Next to its role in protein surveillance, the m-AAA protease processes the ribosomal subunit MrpL32 and is essential for the maturation of the heme-binding reactive oxygen scavenger protein Ccp1 in S. cerevisiae (Esser et al, 2002;Nolden et al, 2005).…”

Section: Introductionmentioning

confidence: 99%

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Them-AAA Protease Processes CytochromecPeroxidase Preferentially at the Inner Boundary Membrane of Mitochondria

Suppanz

Wurm²,

Wenzel

et al. 2009

MBoC

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The m-AAA protease is a conserved hetero-oligomeric complex in the inner membrane of mitochondria. Recent evidence suggests a compartmentalization of the contiguous mitochondrial inner membrane into an inner boundary membrane (IBM) and a cristae membrane (CM). However, little is known about the functional differences of these subdomains. We have analyzed the localizations of the m-AAA protease and its substrate cytochrome c peroxidase (Ccp1) within yeast mitochondria using live cell fluorescence microscopy and quantitative immunoelectron microscopy. We find that the m-AAA protease is preferentially localized in the IBM. Likewise, the membrane-anchored precursor form of Ccp1 accumulates in the IBM of mitochondria lacking a functional m-AAA protease. Only upon proteolytic cleavage the mature form mCcp1 moves into the cristae space. These findings suggest that protein quality control and proteolytic activation exerted by the m-AAA protease take place preferentially in the IBM pointing to significant functional differences between the IBM and the CM.

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Fts H / Hfl B

Bieniossek

Baumann

2004

Handbook of Metalloproteins

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The ATP‐dependent, membrane‐standing metalloprotease FtsH/HflB (filamentation temperature‐sensitive locus H/high frequency of lysogenisation locus B) is universally conserved in eubacteria, chloroplasts, and mitochondria. Its substrates are integral membrane proteins, for example, it degrades the unassembled subunits such as SecY of the SecYEG translocon or the a‐subunit of F o ATPase, as well as some soluble proteins, most notably the heat shock factor σ 32 , the λ‐phage transcriptional activator λ‐CII and LpxC, a key enzyme in lipid A biosynthesis. FtsH is the only essential energy‐dependent protease in Escherichia coli and its knockout shows generally severe phenotypes, for example, malfunctioning of paraplegin, a close homolog in human mitochondria, results in one form of spastic paraplegia. The crystal structure of the cytosolic region reported here reveals a self‐compartmentalizing protease composed of two hexameric rings. The protease ring exhibits perfect sixfold symmetry with a novel, virtually all‐helical fold of the monomers. The active center is formed by the 427 HEAGH motif and the conserved Asp500 as third zing ligand. The AAA domains have ADP bound and are arranged in a hexameric ring with twofold symmetry only. Two of the essential pore residues Phe234, which are implied in substrate binding and translocation, are located toward the interior of the two rings. This suggests a mechanism of substrate recognition and unfolding.

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The m-AAA Protease Defective in Hereditary Spastic Paraplegia Controls Ribosome Assembly in Mitochondria

Cited by 349 publications

References 43 publications

Mitochondrial dynamics in the regulation of neuronal cell death

Mitochondrial dynamics in the regulation of neuronal cell death

Them-AAA Protease Processes CytochromecPeroxidase Preferentially at the Inner Boundary Membrane of Mitochondria

Fts H / Hfl B

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