Hereditary spastic paraplegia: mitochondrial metalloproteases of yeast

Da, Pearce

doi:10.1007/s004390050985

Cited by 12 publications

(6 citation statements)

References 53 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…These proteins are members of the AAA protein superfamily (ATPase associated with diverse cellular activities) which are found widely in both prokaryotic and eukaryotic cells and play an important role in a variety of cellular activities including cell division, transcription, organelle biogenesis, vesicle transport and enzyme assembly (Patel and Latterich, 1998). Yeast mitochondrial ATPases possess both proteolytic and chaperone-like activities at the inner mitochondrial membrane where they are involved in the assembly and degradation of proteins in the respiratory chain complex (Pearce, 1999). Mutation of these genes in yeast induces a respiratory chain defect due to a block in the assembly of the subunits into functional enzymes (Paul and Tzagoloff, 1995).…”

Section: Introductionmentioning

confidence: 99%

A clinical, genetic and biochemical study of SPG7 mutations in hereditary spastic paraplegia

Wilkinson¹

2004

Brain

View full text Add to dashboard Cite

Mutations in the SPG7 gene, encoding the mitochondrial protein paraplegin, were the first to be identified in autosomal recessive hereditary spastic paraplegia (ARHSP). Four different SPG7 mutations have been described so far in association with both pure and complicated HSP phenotypes. Muscle biopsies from the most severely affected patients have shown histological evidence of an oxidative phosphorylation defect. We identified six ARHSP kindreds, in whom linkage to SPG7 could not be excluded, and 29 sporadic spastic paraplegia patients. The 17 exons and flanking regions of the SPG7 gene were screened for mutations using a combination of single-stranded conformation polymorphism (SSCP) analysis and sequencing. Three patients were found to carry compound heterozygous SPG7 mutations, comprising five novel and one previously described mutation. Muscle biopsies from two SPG7 mutation patients did not show any histological evidence of an oxidative phosphorylation defect. However, biochemical analysis revealed a reduction in citrate synthase-corrected complex I and complex II/III activities in muscle and complex I activity in mitochondrial-enriched fractions from cultured myoblasts, suggesting that either a primary or a secondary defect of respiratory chain function may play an important role in the pathogenesis of the disease.

show abstract

Section: Introductionmentioning

confidence: 99%

A clinical, genetic and biochemical study of SPG7 mutations in hereditary spastic paraplegia

Wilkinson¹

2004

Brain

View full text Add to dashboard Cite

show abstract

“…The identification and function of mitochondrial fission and fusion factors in flies and yeast were instrumental to advancements in understanding the mitochondrial defects caused by mutations in their human homologues MFN2 (yeast FZO1 ) that cause Charcot-Marie-Tooth (CMT) subtype 2A, and OPA1 (yeast MGM1) that causes autosomal dominant optic atrophy (ADOA) [163]. Yeast are being applied to the study of multiple additional human neurological disease genes, such as FRDA (yeast YFH1), the cause of Friedreich ataxia [197], Batten disease caused by mutations in human BAN1 (yeast CLN3) [198, 199], Niemann Pick disease caused by a mutation in NPC1 (yeast NCR1) [200, 201], as well as SOD1 in ALS [202], SPG7 (yeast AFG3 and RCA1) in hereditary spastic paraplegia (HSP) [203], ABCD1 (yeast PXA1/2) in X-linked adrenoleukodystrophy (ALD) [204] and many more. However, few have yet exploited yeast for studying programmed cell death related to cancer or other human disorders.…”

Section: Non-mammalian Models Of Human Diseasesmentioning

confidence: 99%

Mitochondrial involvement in cell death of non-mammalian eukaryotes

Abdelwahid

Rolland

Teng

et al. 2011

Biochimica et Biophysica Acta (BBA) - Molecular Cell Research

View full text Add to dashboard Cite

Although mitochondria are essential organelles for long-term survival of eukaryotic cells, recent discoveries in biochemistry and genetics have advanced our understanding of the requirements for mitochondria in cell death. Much of what we understand about cell death is based on the identification of conserved cell death genes in Drosophila melanogaster and Caenorhabditis elegans. However, the role of mitochondria in cell death in these models has been much less clear. Considering the active role that mitochondria play in apoptosis in mammalian cells, the mitochondrial contribution to cell death in non-mammalian systems has been an area of active investigation. In this article, we review the current research on this topic in three non-mammalian models, C. elegans, Drosophila and Saccharomyces cerevisiae. In addition, we discuss how non-mammalian models have provided important insight into the mechanisms of human disease as they relate to the mitochondrial pathway of cell death. The unique perspective derived from each of these model systems provides a more complete understanding of mitochondria in programmed cell death.

show abstract

“…Mas1/2 is the MPP metalloendopeptidase that cleaves presequences from the majority of imported mitochondrial proteins. 29 Oct1 is a matrix intermediate metallopeptidase that cleaves destabilizing N-terminal residues of some proteins after cleavage by MPP. 30 Afg3 is a subunit of the ATP-dependent m-AAA metalloprotease found in the IM.…”

mentioning

confidence: 99%

“…30 Afg3 is a subunit of the ATP-dependent m-AAA metalloprotease found in the IM. 29 Yme1 is the Zn-containing catalytic subunit of the i-AAA metalloprotease complex; this IM enzyme helps degrade unfolded or misfolded mitochondrial proteins. 31 Cym1 and Prd1 are lysine-specific metalloproteases that degrade proteins and presequences.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Labile Low-Molecular-Mass Metal Complexes in Mitochondria: Trials and Tribulations of a Burgeoning Field

Lindahl

Moore

2016

Biochemistry

View full text Add to dashboard Cite

Iron, copper, zinc, manganese, cobalt, and molybdenum play important roles in mitochondrial biochemistry, serving to help catalyze reactions in numerous metalloenzymes. These metals are also found in labile “pools” within mitochondria. Although the composition and cellular function of these pools are largely unknown, they are thought to be comprised of nonproteinaceous low-molecular-mass (LMM) metal complexes. Many problems must be solved before these pools can be fully defined, especially problems stemming from the lability of such complexes. This lability arises from inherently weak coordinate bonds between ligands and metals. This is an advantage for catalysis and trafficking, but it makes characterization difficult. The most popular strategy for investigating such pools is to detect them using chelator probes with fluorescent properties that change upon metal coordination. Characterization is limited because of the inevitable destruction of the complexes during their detection. Moreover, probes likely react with more than one type of metal complex, confusing analyses. An alternative approach is to use liquid chromatography (LC) coupled with inductively coupled plasma mass spectrometry (ICP-MS). With help from a previous lab member, the authors recently developed an LC–ICP-MS approach to analyze LMM extracts from yeast and mammalian mitochondria. They detected several metal complexes, including Fe580, Fe1100, Fe1500, Cu5000, Zn1200, Zn1500, Mn1100, Mn2000, Co1200, Co1500, and Mo780 (numbers refer to approximate masses in daltons). Many of these may be used to metalate apometalloproteins as they fold inside the organelle. The LC-based approach also has challenges, e.g., in distinguishing artifactual metal complexes from endogenous ones, due to the fact that cells must be disrupted to form extracts before they are passed through chromatography columns prior to analysis. Ultimately, both approaches will be needed to characterize these intriguing complexes and to elucidate their roles in mitochondrial biochemistry.

show abstract

Hereditary spastic paraplegia: mitochondrial metalloproteases of yeast

Cited by 12 publications

References 53 publications

A clinical, genetic and biochemical study of SPG7 mutations in hereditary spastic paraplegia

A clinical, genetic and biochemical study of SPG7 mutations in hereditary spastic paraplegia

Mitochondrial involvement in cell death of non-mammalian eukaryotes

Labile Low-Molecular-Mass Metal Complexes in Mitochondria: Trials and Tribulations of a Burgeoning Field

Contact Info

Product

Resources

About