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Matrix Processing Peptidase and Puta...

Torres, Eric Rommel.

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Matrix Processing Peptidase and Putative Roles in Mitochondrial Biogenesis. Nuc1 and Porin influence L-A Killer Virus Loads Co-dependently in Saccharomyces cerevisiae.

Record Type:	Electronic resources : Monograph/item
Title/Author:	Matrix Processing Peptidase and Putative Roles in Mitochondrial Biogenesis. Nuc1 and Porin influence L-A Killer Virus Loads Co-dependently in Saccharomyces cerevisiae./
Author:	Torres, Eric Rommel.
Published:	Ann Arbor : ProQuest Dissertations & Theses, : 2019,
Description:	235 p.
Notes:	Source: Dissertations Abstracts International, Volume: 81-05, Section: B.
Contained By:	Dissertations Abstracts International81-05B.
Subject:	Biochemistry. -
Online resource:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=22621297
ISBN:	9781687921376

Matrix Processing Peptidase and Putative Roles in Mitochondrial Biogenesis. Nuc1 and Porin influence L-A Killer Virus Loads Co-dependently in Saccharomyces cerevisiae.
Torres, Eric Rommel.

Matrix Processing Peptidase and Putative Roles in Mitochondrial Biogenesis. Nuc1 and Porin influence L-A Killer Virus Loads Co-dependently in Saccharomyces cerevisiae. - Ann Arbor : ProQuest Dissertations & Theses, 2019 - 235 p.

Source: Dissertations Abstracts International, Volume: 81-05, Section: B.

Thesis (Ph.D.)--University of California, Los Angeles, 2019.

This item must not be sold to any third party vendors.

Matrix Processing Peptidase and Putative Roles in Mitochondrial BiogenesisThe mitochondrial protein import and proteolytic system are important for homeostasis of the mitochondrion. Typically, precursor proteins are targeted to the mitochondria by an N-terminal targeting sequence and are imported via TOM and TIM translocons of the outer and inner membrane. A series of proteases is required for the import and processing of precursors as well assembly and degradation of mitochondrial proteins. The matrix processing peptidase (MPP) coordinates the removal of presequences from precursors and is important in maintaining mitochondrial homeostasis. Furthermore, MPP is associated with neurodegenerative diseases. A mutation in PMPCA causes a form of non-progressive cerebellar ataxia, because the Friedreich's ataxia protein is not processed correctly. The Parkinson's associated protein PINK1 is processed by MPP and attenuation of β-MPP has been shown to induce mitophagy. To characterize the function of MPP in mammalian systems and develop probes to attenuate MPP function, we developed a small molecule screening strategy to develop MPP-specific chemical probes from a library of over 100,000 drug-like small molecules. The screen yielded two structurally distinct and specific MPP inhibitors deemed MitoBloCK-50 and MitoBloCK-51. Our results suggest in addition to playing a role in the processing of precursors, MPP also plays a role in the import of precursors. Here I present data that characterize the utility of MitoBloCK-50 and MitoBloCK-51 for MPP attenuation in various model systems. In addition, an in vivo tagging system known as BioID identified an interaction between MPP and core subunit Qcr2 of Complex III, suggesting an evolutionary conserved interaction with the respiratory chain.Nuc1 and Porin Influence L-A Viral loads Co-dependently in Saccharomyces cerevisiaeThe yeast double-stranded RNA (dsRNA) killer viruses of the Totiviridae family are well-characterized and one of the most prolific in laboratory yeast strains. Infected yeast are able to tolerate high levels of the killer virus without displaying any growth defects. The complex symbiotic relationship between host yeast and dsRNA viruses are still being elucidated. Notably, deletion of mitochondrial genes NUC1, which encodes the major mitochondrial nuclease, and POR1, the voltage-dependent anion channel of the outer mitochondrial membrane, lead to overproduction of the capsid Gag protein encoded by the L-A dsRNA helper genome of Killer virus. In this work we explore mechanisms of Nuc1 and porin regulation of the L-A dsRNA genome of yeast Killer viruses. We observed strains with NUC1 deletion have higher L-A levels than POR1 deleted strains. Furthermore, deletion of both NUC1 and POR1 have comparable L-A levels to single NUC1 mutants. Plasmid expression of Nuc1 mutants that are nuclease deficient or cytosolic localized fail to rescue L-A viral loads in NUC1 deleted strains. In addition, plasmid expression of NUC1 appears to increase the L-A viral load in the NUC1 and POR1 double knockout. Nuclease protection experiments demonstrate L-A transcripts are protected in ΔNUC1 and ΔPOR1 mitochondria but not in wildtype. We propose a model where ss(+) L-A transcripts are imported into the mitochondrial IMS and are subsequently degraded by Nuc1. Meanwhile, POR1 deletion disrupts the L-A regulating function of Nuc1. Overall these results demonstrate a role for mitochondria in regulating dsRNA viruses in yeast.

ISBN: 9781687921376Subjects--Topical Terms:

518028
Biochemistry.
Subjects--Index Terms:

L-A virus

Matrix Processing Peptidase and Putative Roles in Mitochondrial Biogenesis. Nuc1 and Porin influence L-A Killer Virus Loads Co-dependently in Saccharomyces cerevisiae.
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245 1 0 $a Matrix Processing Peptidase and Putative Roles in Mitochondrial Biogenesis. Nuc1 and Porin influence L-A Killer Virus Loads Co-dependently in Saccharomyces cerevisiae.
260 1 $a Ann Arbor : $b ProQuest Dissertations & Theses, $c 2019
300 $a 235 p.
500 $a Source: Dissertations Abstracts International, Volume: 81-05, Section: B.
500 $a Advisor: Koehler, Carla M.
502 $a Thesis (Ph.D.)--University of California, Los Angeles, 2019.
506 $a This item must not be sold to any third party vendors.
506 $a This item must not be added to any third party search indexes.
520 $a Matrix Processing Peptidase and Putative Roles in Mitochondrial BiogenesisThe mitochondrial protein import and proteolytic system are important for homeostasis of the mitochondrion. Typically, precursor proteins are targeted to the mitochondria by an N-terminal targeting sequence and are imported via TOM and TIM translocons of the outer and inner membrane. A series of proteases is required for the import and processing of precursors as well assembly and degradation of mitochondrial proteins. The matrix processing peptidase (MPP) coordinates the removal of presequences from precursors and is important in maintaining mitochondrial homeostasis. Furthermore, MPP is associated with neurodegenerative diseases. A mutation in PMPCA causes a form of non-progressive cerebellar ataxia, because the Friedreich's ataxia protein is not processed correctly. The Parkinson's associated protein PINK1 is processed by MPP and attenuation of β-MPP has been shown to induce mitophagy. To characterize the function of MPP in mammalian systems and develop probes to attenuate MPP function, we developed a small molecule screening strategy to develop MPP-specific chemical probes from a library of over 100,000 drug-like small molecules. The screen yielded two structurally distinct and specific MPP inhibitors deemed MitoBloCK-50 and MitoBloCK-51. Our results suggest in addition to playing a role in the processing of precursors, MPP also plays a role in the import of precursors. Here I present data that characterize the utility of MitoBloCK-50 and MitoBloCK-51 for MPP attenuation in various model systems. In addition, an in vivo tagging system known as BioID identified an interaction between MPP and core subunit Qcr2 of Complex III, suggesting an evolutionary conserved interaction with the respiratory chain.Nuc1 and Porin Influence L-A Viral loads Co-dependently in Saccharomyces cerevisiaeThe yeast double-stranded RNA (dsRNA) killer viruses of the Totiviridae family are well-characterized and one of the most prolific in laboratory yeast strains. Infected yeast are able to tolerate high levels of the killer virus without displaying any growth defects. The complex symbiotic relationship between host yeast and dsRNA viruses are still being elucidated. Notably, deletion of mitochondrial genes NUC1, which encodes the major mitochondrial nuclease, and POR1, the voltage-dependent anion channel of the outer mitochondrial membrane, lead to overproduction of the capsid Gag protein encoded by the L-A dsRNA helper genome of Killer virus. In this work we explore mechanisms of Nuc1 and porin regulation of the L-A dsRNA genome of yeast Killer viruses. We observed strains with NUC1 deletion have higher L-A levels than POR1 deleted strains. Furthermore, deletion of both NUC1 and POR1 have comparable L-A levels to single NUC1 mutants. Plasmid expression of Nuc1 mutants that are nuclease deficient or cytosolic localized fail to rescue L-A viral loads in NUC1 deleted strains. In addition, plasmid expression of NUC1 appears to increase the L-A viral load in the NUC1 and POR1 double knockout. Nuclease protection experiments demonstrate L-A transcripts are protected in ΔNUC1 and ΔPOR1 mitochondria but not in wildtype. We propose a model where ss(+) L-A transcripts are imported into the mitochondrial IMS and are subsequently degraded by Nuc1. Meanwhile, POR1 deletion disrupts the L-A regulating function of Nuc1. Overall these results demonstrate a role for mitochondria in regulating dsRNA viruses in yeast.
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650 4 $a Molecular biology. $3 517296
650 4 $a Physiology. $3 518431
650 4 $a Health sciences. $3 3168359
653 $a L-A virus
653 $a Matrix Processing Peptidase
653 $a Mitochondria
653 $a MPP
653 $a Nuc1
653 $a Por1
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690 $a 0307
690 $a 0566
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710 2 $a University of California, Los Angeles. $b Biochemistry & Molecular Biology 0114. $3 3286027
773 0 $t Dissertations Abstracts International $g 81-05B.
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791 $a Ph.D.
792 $a 2019
793 $a English
856 4 0 $u http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=22621297