The MAS-encoded processing protease of yeast mitochondria. Interaction of the purified enzyme with signal peptides and a purified precursor protein.

Yang, Meng; Géli, Vincent; Oppliger, Wolfgang; Suda, Kitaru; James, Pranee; Schatz, Gottfried

doi:10.1016/s0021-9258(18)38134-1

Cited by 72 publications

(15 citation statements)

References 44 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…SD, standard deviation; SOD, superoxide dismutase enzyme; WT, wild-type promoting further accumulation of immature proteins. 51 In addition to interfering with MPP activity, presequence peptides have been proposed to form pores in the mitochondrial inner membrane, leading dissipation of membrane potential, and limiting respiration. [52][53][54] In addition to the defect observed for Sod2p content, sdo1Δ cells exhibit elevated accumulation of the VDAC Por1p.…”

Section: Discussionmentioning

confidence: 99%

Decreased accumulation of superoxide dismutase 2 within mitochondria in the yeast model of Shwachman‐Diamond syndrome

Jensen

Jain

Kaewwanna

et al. 2019

J of Cellular Biochemistry

View full text Add to dashboard Cite

Mutations in the human SBDS gene is the most common cause of Shwachman-Diamond syndrome (SDS). The SBDS protein participates in ribosome biogenesis; however, effects beyond reduced translation efficiency are thought to be involved in SDS progression. Impaired mitochondrial function has been reported for cells lacking either SBDS or Sdo1p, the Saccharomyces cerevisiae SBDS ortholog. To better understand how the loss of SBDS/Sdo1p leads to mitochondria damage, we utilized the S. cerevisiae model of SDS. Yeast deleted for SDO1 show increased oxidative damage to mitochondrial proteins and a marked decrease in protein levels and activity of mitochondrial superoxide dismutase 2 (Sod2p), a key enzyme involved in defense against oxidants.Immature forms of Sod2p are observed in sdo1Δ cells suggesting a defect in proteolysis of the presequence. Yeast deleted for CYM1, encoding a presequence protease, display a similar reduction in Sod2p activity as sdo1Δ cells, as well as elevated oxidative damage, to mitochondrial proteins. Sod2p protein levels and activity are largely restored in a por1Δ sdo1Δ strain, lacking the major mitochondrial voltage-dependent anion channel. Together these results indicate that mitochondrial insufficiency in sdo1Δ cells may be linked to the accumulation of immature presequence containing proteins and this effect is a consequence, at least in part, from loss of counter-regulation of Por1p by Sdo1p. K E Y W O R D Smitochondria, oxidative stress, Shwachman-Diamond syndrome, superoxide dismutase, yeast

show abstract

Section: Discussionmentioning

confidence: 99%

Decreased accumulation of superoxide dismutase 2 within mitochondria in the yeast model of Shwachman‐Diamond syndrome

Jensen

Jain

Kaewwanna

et al. 2019

J of Cellular Biochemistry

View full text Add to dashboard Cite

show abstract

“…the precursor by the matrix processing peptidase (MPP), giving rise to the mature mitochondrial protein (Yang et al, 1991).…”

Section: Protein Sorting In the Inner Mitochondrial Compartmentsmentioning

confidence: 99%

“…Protein transport into the matrix requires the ATP-dependent activity of the mitochondrial heat shock protein 70 (mtHsp70) ( Pais et al, 2011 ) in addition to the membrane potential. Once in the matrix, the presequence is cleaved off from the precursor by the matrix processing peptidase (MPP), giving rise to the mature mitochondrial protein ( Yang et al, 1991 ).…”

Section: Overview Of Mitochondrial Protein Import Pathwaysmentioning

confidence: 99%

Redox-Mediated Regulation of Mitochondrial Biogenesis, Dynamics, and Respiratory Chain Assembly in Yeast and Human Cells

Geldon

Fernández-Vizarra

Tokatlidis

2021

Front. Cell Dev. Biol.

View full text Add to dashboard Cite

Mitochondria are double-membrane organelles that contain their own genome, the mitochondrial DNA (mtDNA), and reminiscent of its endosymbiotic origin. Mitochondria are responsible for cellular respiration via the function of the electron oxidative phosphorylation system (OXPHOS), located in the mitochondrial inner membrane and composed of the four electron transport chain (ETC) enzymes (complexes I-IV), and the ATP synthase (complex V). Even though the mtDNA encodes essential OXPHOS components, the large majority of the structural subunits and additional biogenetical factors (more than seventy proteins) are encoded in the nucleus and translated in the cytoplasm. To incorporate these proteins and the rest of the mitochondrial proteome, mitochondria have evolved varied, and sophisticated import machineries that specifically target proteins to the different compartments defined by the two membranes. The intermembrane space (IMS) contains a high number of cysteine-rich proteins, which are mostly imported via the MIA40 oxidative folding system, dependent on the reduction, and oxidation of key Cys residues. Several of these proteins are structural components or assembly factors necessary for the correct maturation and function of the ETC complexes. Interestingly, many of these proteins are involved in the metalation of the active redox centers of complex IV, the terminal oxidase of the mitochondrial ETC. Due to their function in oxygen reduction, mitochondria are the main generators of reactive oxygen species (ROS), on both sides of the inner membrane, i.e., in the matrix and the IMS. ROS generation is important due to their role as signaling molecules, but an excessive production is detrimental due to unwanted oxidation reactions that impact on the function of different types of biomolecules contained in mitochondria. Therefore, the maintenance of the redox balance in the IMS is essential for mitochondrial function. In this review, we will discuss the role that redox regulation plays in the maintenance of IMS homeostasis as well as how mitochondrial ROS generation may be a key regulatory factor for ETC biogenesis, especially for complex IV.

show abstract

“…PreP was initially identified in Arabidopsis thaliana (AtPreP), and shown to degrade the MTS of both mitochondria and chloroplasts [38]. A yeast mutant lacking the PITRM1 homolog Cym1 [39] displayed mitochondrial accumulation of precursor proteins and processing intermediates, as well as decreased levels of cleaved, mature proteins [32,40]. Impaired preprotein maturation leads to accelerated protein degradation and an unbalanced mitochondrial proteome, resulting in mitochondrial dysfunction manifested by reduced respiration, altered membrane potential, and high ROS levels [28,37].…”

Section: Pitrm1/prepmentioning

confidence: 99%

“…Other ATP-independent proteases such as the mitochondrial processing peptidase (MPP), the mitochondrial intermediate protease (MIP), and the inner membrane peptidase (IMP), also generate short peptides. Upon import of the mitochondrial precursor proteins, MPP in the matrix cleaves the MTSs, releasing the mature proteins [31][32][33]. MPP activity can produce import intermediates, which are further processed by MIP (the octapeptidyl peptidase Oct1 in yeast) or IMP (the intermediate cleaving peptidase Icp55 in yeast) [33][34][35][36].…”

Section: Introductionmentioning

confidence: 99%

Role of PITRM1 in Mitochondrial Dysfunction and Neurodegeneration

et al. 2021

View full text Add to dashboard Cite

Mounting evidence shows a link between mitochondrial dysfunction and neurodegenerative disorders, including Alzheimer Disease. Increased oxidative stress, defective mitodynamics, and impaired oxidative phosphorylation leading to decreased ATP production, can determine synaptic dysfunction, apoptosis, and neurodegeneration. Furthermore, mitochondrial proteostasis and the protease-mediated quality control system, carrying out degradation of potentially toxic peptides and misfolded or damaged proteins inside mitochondria, are emerging as potential pathogenetic mechanisms. The enzyme pitrilysin metallopeptidase 1 (PITRM1) is a key player in these processes; it is responsible for degrading mitochondrial targeting sequences that are cleaved off from the imported precursor proteins and for digesting a mitochondrial fraction of amyloid beta (Aβ). In this review, we present current evidence obtained from patients with PITRM1 mutations, as well as the different cellular and animal models of PITRM1 deficiency, which points toward PITRM1 as a possible driving factor of several neurodegenerative conditions. Finally, we point out the prospect of new diagnostic and therapeutic approaches.

show abstract

The MAS-encoded processing protease of yeast mitochondria. Interaction of the purified enzyme with signal peptides and a purified precursor protein.

Cited by 72 publications

References 44 publications

Decreased accumulation of superoxide dismutase 2 within mitochondria in the yeast model of Shwachman‐Diamond syndrome

Decreased accumulation of superoxide dismutase 2 within mitochondria in the yeast model of Shwachman‐Diamond syndrome

Redox-Mediated Regulation of Mitochondrial Biogenesis, Dynamics, and Respiratory Chain Assembly in Yeast and Human Cells

Role of PITRM1 in Mitochondrial Dysfunction and Neurodegeneration

Contact Info

Product

Resources

About