Sex-dependent Differences in the Bioenergetics of Liver and Muscle Mitochondria from Mice Containing a Deletion for glutaredoxin-2.
Identifieur interne : 000122 ( Main/Exploration ); précédent : 000121; suivant : 000123Sex-dependent Differences in the Bioenergetics of Liver and Muscle Mitochondria from Mice Containing a Deletion for glutaredoxin-2.
Auteurs : Sarah Mallay [Canada] ; Robert Gill [Canada] ; Adrian Young [Canada] ; Ryan J. Mailloux [Canada]Source :
- Antioxidants (Basel, Switzerland) [ 2076-3921 ] ; 2019.
Abstract
Our group recently published a study demonstrating that deleting the gene encoding the matrix thiol oxidoreductase, glutaredoxin-2 (GRX2), alters the bioenergetics of mitochondria isolated from male C57BL/6N mice. Here, we conducted a similar study, examining H2O2 production and respiration in mitochondria isolated from female mice heterozygous (GRX2+/-) or homozygous (GRX2-/-) for glutaredoxin-2. First, we observed that deleting the Grx2 gene does not alter the rate of H2O2 production in liver and muscle mitochondria oxidizing pyruvate, α-ketoglutarate, or succinate. Examination of the rates of H2O2 release from liver mitochondria isolated from male and female mice revealed that (1) sex has an impact on the rate of ROS production by liver and muscle mitochondria and (2) loss of GRX2 only altered ROS release in mitochondria collected from male mice. Assessment of the bioenergetics of these mitochondria revealed that loss of GRX2 increased proton leak-dependent and phosphorylating respiration in liver mitochondria isolated from female mice but did not alter rates of respiration in liver mitochondria from male mice. Furthermore, we found that deleting the Grx2 gene did not alter rates of respiration in muscle mitochondria collected from female mice. This contrasts with male mice where loss of GRX2 substantially augmented proton leaks and ADP-stimulated respiration. Our findings indicate that some fundamental sexual dimorphisms exist between GRX2-deficient male and female rodents.
DOI: 10.3390/antiox8080245
PubMed: 31357416
PubMed Central: PMC6720827
Affiliations:
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Mailloux</name><affiliation wicri:level="1"><nlm:affiliation>Department of Biochemistry, Memorial University of Newfoundland, St. John's, NL A1B 3X7, Canada. rjmailloux@mun.ca.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>Department of Biochemistry, Memorial University of Newfoundland, St. John's, NL A1B 3X7</wicri:regionArea><wicri:noRegion>NL A1B 3X7</wicri:noRegion></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2019">2019</date><idno type="RBID">pubmed:31357416</idno><idno type="pmid">31357416</idno><idno type="doi">10.3390/antiox8080245</idno><idno type="pmc">PMC6720827</idno><idno type="wicri:Area/Main/Corpus">000124</idno><idno type="wicri:explorRef" wicri:stream="Main" wicri:step="Corpus" wicri:corpus="PubMed">000124</idno><idno type="wicri:Area/Main/Curation">000124</idno><idno type="wicri:explorRef" wicri:stream="Main" wicri:step="Curation">000124</idno><idno type="wicri:Area/Main/Exploration">000124</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">Sex-dependent Differences in the Bioenergetics of Liver and Muscle Mitochondria from Mice Containing a Deletion for <i>glutaredoxin-2</i>.</title><author><name sortKey="Mallay, Sarah" sort="Mallay, Sarah" uniqKey="Mallay S" first="Sarah" last="Mallay">Sarah Mallay</name><affiliation wicri:level="1"><nlm:affiliation>Department of Biochemistry, Memorial University of Newfoundland, St. John's, NL A1B 3X7, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>Department of Biochemistry, Memorial University of Newfoundland, St. John's, NL A1B 3X7</wicri:regionArea><wicri:noRegion>NL A1B 3X7</wicri:noRegion></affiliation></author><author><name sortKey="Gill, Robert" sort="Gill, Robert" uniqKey="Gill R" first="Robert" last="Gill">Robert Gill</name><affiliation wicri:level="1"><nlm:affiliation>Department of Biochemistry, Memorial University of Newfoundland, St. John's, NL A1B 3X7, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>Department of Biochemistry, Memorial University of Newfoundland, St. John's, NL A1B 3X7</wicri:regionArea><wicri:noRegion>NL A1B 3X7</wicri:noRegion></affiliation></author><author><name sortKey="Young, Adrian" sort="Young, Adrian" uniqKey="Young A" first="Adrian" last="Young">Adrian Young</name><affiliation wicri:level="1"><nlm:affiliation>Department of Biochemistry, Memorial University of Newfoundland, St. John's, NL A1B 3X7, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>Department of Biochemistry, Memorial University of Newfoundland, St. John's, NL A1B 3X7</wicri:regionArea><wicri:noRegion>NL A1B 3X7</wicri:noRegion></affiliation></author><author><name sortKey="Mailloux, Ryan J" sort="Mailloux, Ryan J" uniqKey="Mailloux R" first="Ryan J" last="Mailloux">Ryan J. Mailloux</name><affiliation wicri:level="1"><nlm:affiliation>Department of Biochemistry, Memorial University of Newfoundland, St. John's, NL A1B 3X7, Canada. rjmailloux@mun.ca.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>Department of Biochemistry, Memorial University of Newfoundland, St. John's, NL A1B 3X7</wicri:regionArea><wicri:noRegion>NL A1B 3X7</wicri:noRegion></affiliation></author></analytic><series><title level="j">Antioxidants (Basel, Switzerland)</title><idno type="ISSN">2076-3921</idno><imprint><date when="2019" type="published">2019</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Our group recently published a study demonstrating that deleting the gene encoding the matrix thiol oxidoreductase, glutaredoxin-2 (GRX2), alters the bioenergetics of mitochondria isolated from male C57BL/6N mice. Here, we conducted a similar study, examining H<sub>2</sub>O<sub>2</sub> production and respiration in mitochondria isolated from female mice heterozygous (GRX2+/-) or homozygous (GRX2-/-) for glutaredoxin-2. First, we observed that deleting the <i>Grx2</i> gene does not alter the rate of H<sub>2</sub>O<sub>2</sub> production in liver and muscle mitochondria oxidizing pyruvate, α-ketoglutarate, or succinate. Examination of the rates of H<sub>2</sub>O<sub>2</sub> release from liver mitochondria isolated from male and female mice revealed that (1) sex has an impact on the rate of ROS production by liver and muscle mitochondria and (2) loss of GRX2 only altered ROS release in mitochondria collected from male mice. Assessment of the bioenergetics of these mitochondria revealed that loss of GRX2 increased proton leak-dependent and phosphorylating respiration in liver mitochondria isolated from female mice but did not alter rates of respiration in liver mitochondria from male mice. Furthermore, we found that deleting the <i>Grx2</i> gene did not alter rates of respiration in muscle mitochondria collected from female mice. This contrasts with male mice where loss of GRX2 substantially augmented proton leaks and ADP-stimulated respiration. Our findings indicate that some fundamental sexual dimorphisms exist between GRX2-deficient male and female rodents.</div></front></TEI><pubmed><MedlineCitation Status="PubMed-not-MEDLINE" Owner="NLM"><PMID Version="1">31357416</PMID><DateRevised><Year>2020</Year><Month>09</Month><Day>30</Day></DateRevised><Article PubModel="Electronic"><Journal><ISSN IssnType="Print">2076-3921</ISSN><JournalIssue CitedMedium="Print"><Volume>8</Volume><Issue>8</Issue><PubDate><Year>2019</Year><Month>Jul</Month><Day>26</Day></PubDate></JournalIssue><Title>Antioxidants (Basel, Switzerland)</Title><ISOAbbreviation>Antioxidants (Basel)</ISOAbbreviation></Journal><ArticleTitle>Sex-dependent Differences in the Bioenergetics of Liver and Muscle Mitochondria from Mice Containing a Deletion for <i>glutaredoxin-2</i>.</ArticleTitle><ELocationID EIdType="pii" ValidYN="Y">E245</ELocationID><ELocationID EIdType="doi" ValidYN="Y">10.3390/antiox8080245</ELocationID><Abstract><AbstractText>Our group recently published a study demonstrating that deleting the gene encoding the matrix thiol oxidoreductase, glutaredoxin-2 (GRX2), alters the bioenergetics of mitochondria isolated from male C57BL/6N mice. Here, we conducted a similar study, examining H<sub>2</sub>O<sub>2</sub> production and respiration in mitochondria isolated from female mice heterozygous (GRX2+/-) or homozygous (GRX2-/-) for glutaredoxin-2. First, we observed that deleting the <i>Grx2</i> gene does not alter the rate of H<sub>2</sub>O<sub>2</sub> production in liver and muscle mitochondria oxidizing pyruvate, α-ketoglutarate, or succinate. Examination of the rates of H<sub>2</sub>O<sub>2</sub> release from liver mitochondria isolated from male and female mice revealed that (1) sex has an impact on the rate of ROS production by liver and muscle mitochondria and (2) loss of GRX2 only altered ROS release in mitochondria collected from male mice. Assessment of the bioenergetics of these mitochondria revealed that loss of GRX2 increased proton leak-dependent and phosphorylating respiration in liver mitochondria isolated from female mice but did not alter rates of respiration in liver mitochondria from male mice. Furthermore, we found that deleting the <i>Grx2</i> gene did not alter rates of respiration in muscle mitochondria collected from female mice. This contrasts with male mice where loss of GRX2 substantially augmented proton leaks and ADP-stimulated respiration. Our findings indicate that some fundamental sexual dimorphisms exist between GRX2-deficient male and female rodents.</AbstractText></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Mallay</LastName><ForeName>Sarah</ForeName><Initials>S</Initials><AffiliationInfo><Affiliation>Department of Biochemistry, Memorial University of Newfoundland, St. John's, NL A1B 3X7, Canada.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Gill</LastName><ForeName>Robert</ForeName><Initials>R</Initials><AffiliationInfo><Affiliation>Department of Biochemistry, Memorial University of Newfoundland, St. John's, NL A1B 3X7, Canada.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Young</LastName><ForeName>Adrian</ForeName><Initials>A</Initials><AffiliationInfo><Affiliation>Department of Biochemistry, Memorial University of Newfoundland, St. John's, NL A1B 3X7, Canada.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Mailloux</LastName><ForeName>Ryan J</ForeName><Initials>RJ</Initials><Identifier Source="ORCID">0000-0003-3986-9830</Identifier><AffiliationInfo><Affiliation>Department of Biochemistry, Memorial University of Newfoundland, St. John's, NL A1B 3X7, Canada. rjmailloux@mun.ca.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><GrantList CompleteYN="Y"><Grant><GrantID>RGPIN-2016-04829</GrantID><Agency>Natural Sciences and Engineering Research Council of Canada</Agency><Country></Country></Grant></GrantList><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2019</Year><Month>07</Month><Day>26</Day></ArticleDate></Article><MedlineJournalInfo><Country>Switzerland</Country><MedlineTA>Antioxidants (Basel)</MedlineTA><NlmUniqueID>101668981</NlmUniqueID><ISSNLinking>2076-3921</ISSNLinking></MedlineJournalInfo><KeywordList Owner="NOTNLM"><Keyword 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