Beneficial effects of SS-31 peptide on cardiac mitochondrial dysfunction in tafazzin knockdown mice.
| Title: | Beneficial effects of SS-31 peptide on cardiac mitochondrial dysfunction in tafazzin knockdown mice. |
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| Authors: | Russo, Silvia1 (AUTHOR), De Rasmo, Domenico2 (AUTHOR), Signorile, Anna1 (AUTHOR), Corcelli, Angela1 (AUTHOR), Lobasso, Simona1 (AUTHOR) simona.lobasso@uniba.it |
| Source: | Scientific Reports. 11/18/2022, Vol. 12 Issue 1, p1-14. 14p. |
| Subject Terms: | *PEPTIDES, *MICE, *GENETIC disorders, *PHOSPHOLIPIDS, *THERAPEUTICS, *CARDIOLIPIN, *PLANT mitochondria |
| Abstract: | Barth Syndrome (BTHS), a genetic disease associated with early-onset cardioskeletal myopathy, is caused by loss-of-function mutations of the TAFAZZIN gene, which is responsible for remodeling the mitochondrial phospholipid cardiolipin (CL). Deregulation of CL biosynthesis and maturation in BTHS mitochondria result in a dramatically increased monolysocardiolipin (MLCL)/CL ratio associated with bioenergetic dysfunction. One of the most promising therapeutic approaches for BTHS includes the mitochondria-targeted tetrapeptide SS-31, which interacts with CL. Here, we used TAFAZZIN knockdown (TazKD) mice to investigate for the first time whether in vivo administration of SS-31 could affect phospholipid profiles and mitochondrial dysfunction. The CL fingerprinting of TazKD cardiac mitochondria obtained by MALDI-TOF/MS revealed the typical lipid changes associated with BTHS. TazKD mitochondria showed lower respiratory rates in state 3 and 4 together with a decreased in maximal respiratory rates. Treatment of TazKD mice with SS-31 improved mitochondrial respiratory capacity and promoted supercomplex organization, without affecting the MLCL/CL ratio. We hypothesize that SS-31 exerts its effect by influencing the function of the respiratory chain rather than affecting CL directly. In conclusion, our results indicate that SS-31 have beneficial effects on improving cardiac mitochondrial dysfunction in a BTHS animal model, suggesting the peptide as future pharmacologic agent for therapy. [ABSTRACT FROM AUTHOR] |
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| Items | – Name: Title Label: Title Group: Ti Data: Beneficial effects of SS-31 peptide on cardiac mitochondrial dysfunction in tafazzin knockdown mice. – Name: Author Label: Authors Group: Au Data: <searchLink fieldCode="AR" term="%22Russo%2C+Silvia%22">Russo, Silvia</searchLink><relatesTo>1</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22De+Rasmo%2C+Domenico%22">De Rasmo, Domenico</searchLink><relatesTo>2</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Signorile%2C+Anna%22">Signorile, Anna</searchLink><relatesTo>1</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Corcelli%2C+Angela%22">Corcelli, Angela</searchLink><relatesTo>1</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Lobasso%2C+Simona%22">Lobasso, Simona</searchLink><relatesTo>1</relatesTo> (AUTHOR)<i> simona.lobasso@uniba.it</i> – Name: TitleSource Label: Source Group: Src Data: <searchLink fieldCode="JN" term="%22Scientific+Reports%22">Scientific Reports</searchLink>. 11/18/2022, Vol. 12 Issue 1, p1-14. 14p. – Name: Subject Label: Subject Terms Group: Su Data: *<searchLink fieldCode="DE" term="%22PEPTIDES%22">PEPTIDES</searchLink><br />*<searchLink fieldCode="DE" term="%22MICE%22">MICE</searchLink><br />*<searchLink fieldCode="DE" term="%22GENETIC+disorders%22">GENETIC disorders</searchLink><br />*<searchLink fieldCode="DE" term="%22PHOSPHOLIPIDS%22">PHOSPHOLIPIDS</searchLink><br />*<searchLink fieldCode="DE" term="%22THERAPEUTICS%22">THERAPEUTICS</searchLink><br />*<searchLink fieldCode="DE" term="%22CARDIOLIPIN%22">CARDIOLIPIN</searchLink><br />*<searchLink fieldCode="DE" term="%22PLANT+mitochondria%22">PLANT mitochondria</searchLink> – Name: Abstract Label: Abstract Group: Ab Data: Barth Syndrome (BTHS), a genetic disease associated with early-onset cardioskeletal myopathy, is caused by loss-of-function mutations of the TAFAZZIN gene, which is responsible for remodeling the mitochondrial phospholipid cardiolipin (CL). Deregulation of CL biosynthesis and maturation in BTHS mitochondria result in a dramatically increased monolysocardiolipin (MLCL)/CL ratio associated with bioenergetic dysfunction. One of the most promising therapeutic approaches for BTHS includes the mitochondria-targeted tetrapeptide SS-31, which interacts with CL. Here, we used TAFAZZIN knockdown (TazKD) mice to investigate for the first time whether in vivo administration of SS-31 could affect phospholipid profiles and mitochondrial dysfunction. The CL fingerprinting of TazKD cardiac mitochondria obtained by MALDI-TOF/MS revealed the typical lipid changes associated with BTHS. TazKD mitochondria showed lower respiratory rates in state 3 and 4 together with a decreased in maximal respiratory rates. Treatment of TazKD mice with SS-31 improved mitochondrial respiratory capacity and promoted supercomplex organization, without affecting the MLCL/CL ratio. We hypothesize that SS-31 exerts its effect by influencing the function of the respiratory chain rather than affecting CL directly. In conclusion, our results indicate that SS-31 have beneficial effects on improving cardiac mitochondrial dysfunction in a BTHS animal model, suggesting the peptide as future pharmacologic agent for therapy. [ABSTRACT FROM AUTHOR] – Name: AbstractSuppliedCopyright Label: Group: Ab Data: <i>Copyright of Scientific Reports is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.) |
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| RecordInfo | BibRecord: BibEntity: Identifiers: – Type: doi Value: 10.1038/s41598-022-24231-4 Languages: – Code: eng Text: English PhysicalDescription: Pagination: PageCount: 14 StartPage: 1 Subjects: – SubjectFull: PEPTIDES Type: general – SubjectFull: MICE Type: general – SubjectFull: GENETIC disorders Type: general – SubjectFull: PHOSPHOLIPIDS Type: general – SubjectFull: THERAPEUTICS Type: general – SubjectFull: CARDIOLIPIN Type: general – SubjectFull: PLANT mitochondria Type: general Titles: – TitleFull: Beneficial effects of SS-31 peptide on cardiac mitochondrial dysfunction in tafazzin knockdown mice. Type: main BibRelationships: HasContributorRelationships: – PersonEntity: Name: NameFull: Russo, Silvia – PersonEntity: Name: NameFull: De Rasmo, Domenico – PersonEntity: Name: NameFull: Signorile, Anna – PersonEntity: Name: NameFull: Corcelli, Angela – PersonEntity: Name: NameFull: Lobasso, Simona IsPartOfRelationships: – BibEntity: Dates: – D: 18 M: 11 Text: 11/18/2022 Type: published Y: 2022 Identifiers: – Type: issn-print Value: 20452322 Numbering: – Type: volume Value: 12 – Type: issue Value: 1 Titles: – TitleFull: Scientific Reports Type: main |
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