An upstream open reading frame regulates expression of the mitochondrial protein Slm35 and mitophagy flux.
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| Title: | An upstream open reading frame regulates expression of the mitochondrial protein Slm35 and mitophagy flux. |
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| Authors: | Romo‐Casanueva, Hernán1 (AUTHOR), Mendoza‐Martínez, Ariann E.1 (AUTHOR), Medina‐Flores, P. Abril1 (AUTHOR), Campero‐Basaldua, Carlos2 (AUTHOR), DeLuna, Alexander3,4 (AUTHOR), Funes, Soledad1 (AUTHOR) sfunes@ifc.unam.mx |
| Source: | FEBS Letters. Jun2026, Vol. 600 Issue 12, p1782-1800. 19p. |
| Subjects: | Open reading frames (Genetics), Mitochondrial proteins, Saccharomyces cerevisiae, Autophagy, Physiological stress, Protein synthesis |
| Abstract: | Mitochondrial protein Slm35 is linked to TOR1 signaling, mitophagy, and stress response in Saccharomyces cerevisiae. Nonetheless, little is known about its regulation or how it affects stress adaptation. In this work, we identified stress‐related transcription factor binding sites and two upstream open reading frames (uORFs) in the 5′‐UTR of SLM35. Using transcriptional reporters, we showed that the transcription factor Gis1 represses SLM35 transcription; however, Slm35 protein levels increased under oxidative stress and in early stationary phase, suggesting post‐transcriptional regulation. Site‐directed mutagenesis revealed that one uORF negatively regulates translation, with its disruption leading to altered Slm35 levels and a reproducible increase in mitophagy flux. These findings reveal multilayered control of SLM35 expression and underscore the role of uORF‐mediated translation in mitochondrial stress responses. Impact statementThis study shows that SLM35, encoding a mitochondrial protein, is controlled through multiple regulatory layers, combining transcriptional repression by stress‐responsive factors with uORF‐mediated translational regulation. By linking these mechanisms to mitophagy, the work provides new insight into mitochondrial quality control under stress. [ABSTRACT FROM AUTHOR] |
| Copyright of FEBS Letters is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. 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. (Copyright applies to all Abstracts.) | |
| Database: | Engineering Source |
| FullText | Text: Availability: 0 |
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| Header | DbId: egs DbLabel: Engineering Source An: 194752990 AccessLevel: 6 PubType: Academic Journal PubTypeId: academicJournal PreciseRelevancyScore: 0 |
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| Items | – Name: Title Label: Title Group: Ti Data: An upstream open reading frame regulates expression of the mitochondrial protein Slm35 and mitophagy flux. – Name: Author Label: Authors Group: Au Data: <searchLink fieldCode="AR" term="%22Romo‐Casanueva%2C+Hernán%22">Romo‐Casanueva, Hernán</searchLink><relatesTo>1</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Mendoza‐Martínez%2C+Ariann+E%2E%22">Mendoza‐Martínez, Ariann E.</searchLink><relatesTo>1</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Medina‐Flores%2C+P%2E+Abril%22">Medina‐Flores, P. Abril</searchLink><relatesTo>1</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Campero‐Basaldua%2C+Carlos%22">Campero‐Basaldua, Carlos</searchLink><relatesTo>2</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22DeLuna%2C+Alexander%22">DeLuna, Alexander</searchLink><relatesTo>3,4</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Funes%2C+Soledad%22">Funes, Soledad</searchLink><relatesTo>1</relatesTo> (AUTHOR)<i> sfunes@ifc.unam.mx</i> – Name: TitleSource Label: Source Group: Src Data: <searchLink fieldCode="JN" term="%22FEBS+Letters%22">FEBS Letters</searchLink>. Jun2026, Vol. 600 Issue 12, p1782-1800. 19p. – Name: Subject Label: Subjects Group: Su Data: <searchLink fieldCode="DE" term="%22Open+reading+frames+%28Genetics%29%22">Open reading frames (Genetics)</searchLink><br /><searchLink fieldCode="DE" term="%22Mitochondrial+proteins%22">Mitochondrial proteins</searchLink><br /><searchLink fieldCode="DE" term="%22Saccharomyces+cerevisiae%22">Saccharomyces cerevisiae</searchLink><br /><searchLink fieldCode="DE" term="%22Autophagy%22">Autophagy</searchLink><br /><searchLink fieldCode="DE" term="%22Physiological+stress%22">Physiological stress</searchLink><br /><searchLink fieldCode="DE" term="%22Protein+synthesis%22">Protein synthesis</searchLink> – Name: Abstract Label: Abstract Group: Ab Data: Mitochondrial protein Slm35 is linked to TOR1 signaling, mitophagy, and stress response in Saccharomyces cerevisiae. Nonetheless, little is known about its regulation or how it affects stress adaptation. In this work, we identified stress‐related transcription factor binding sites and two upstream open reading frames (uORFs) in the 5′‐UTR of SLM35. Using transcriptional reporters, we showed that the transcription factor Gis1 represses SLM35 transcription; however, Slm35 protein levels increased under oxidative stress and in early stationary phase, suggesting post‐transcriptional regulation. Site‐directed mutagenesis revealed that one uORF negatively regulates translation, with its disruption leading to altered Slm35 levels and a reproducible increase in mitophagy flux. These findings reveal multilayered control of SLM35 expression and underscore the role of uORF‐mediated translation in mitochondrial stress responses. Impact statementThis study shows that SLM35, encoding a mitochondrial protein, is controlled through multiple regulatory layers, combining transcriptional repression by stress‐responsive factors with uORF‐mediated translational regulation. By linking these mechanisms to mitophagy, the work provides new insight into mitochondrial quality control under stress. [ABSTRACT FROM AUTHOR] – Name: AbstractSuppliedCopyright Label: Group: Ab Data: <i>Copyright of FEBS Letters is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. 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: 10.1002/1873-3468.70269 Languages: – Code: eng Text: English PhysicalDescription: Pagination: PageCount: 19 StartPage: 1782 Subjects: – SubjectFull: Open reading frames (Genetics) Type: general – SubjectFull: Mitochondrial proteins Type: general – SubjectFull: Saccharomyces cerevisiae Type: general – SubjectFull: Autophagy Type: general – SubjectFull: Physiological stress Type: general – SubjectFull: Protein synthesis Type: general Titles: – TitleFull: An upstream open reading frame regulates expression of the mitochondrial protein Slm35 and mitophagy flux. Type: main BibRelationships: HasContributorRelationships: – PersonEntity: Name: NameFull: Romo‐Casanueva, Hernán – PersonEntity: Name: NameFull: Mendoza‐Martínez, Ariann E. – PersonEntity: Name: NameFull: Medina‐Flores, P. Abril – PersonEntity: Name: NameFull: Campero‐Basaldua, Carlos – PersonEntity: Name: NameFull: DeLuna, Alexander – PersonEntity: Name: NameFull: Funes, Soledad IsPartOfRelationships: – BibEntity: Dates: – D: 15 M: 06 Text: Jun2026 Type: published Y: 2026 Identifiers: – Type: issn-print Value: 00145793 Numbering: – Type: volume Value: 600 – Type: issue Value: 12 Titles: – TitleFull: FEBS Letters Type: main |
| ResultId | 1 |
