Inactivation of HAP4 accelerates RTG-dependent Osmoadaptation in Saccharomyces cerevisiae
Open accessAbstract
Mitochondrial RTG (an acronym for ReTroGrade) signaling plays a cytoprotective role under various intracellular or environmental stresses. We have previously shown its contribution to osmoadaptation and capacity to sustain mitochondrial respiration in yeast. Here, we studied the interplay between RTG2, the main positive regulator of the RTG pathway, and HAP4, encoding the catalytic subunit of the Hap2-5 complex required for the expression of many mitochondrial proteins that function in the tricarboxylic acid (TCA) cycle and electron transport, upon osmotic stress. Cell growth features, mitochondrial respiratory competence, retrograde signaling activation, and TCA cycle gene expression were comparatively evaluated in wild type and mutant cells in the presence and in the absence of salt stress. We showed that the inactivation of HAP4 improved the kinetics of osmoadaptation by eliciting both the activation of retrograde signaling and the upregulation of three TCA cycle genes: citrate synthase 1 (CIT1), aconitase 1 (ACO1), and isocitrate dehydrogenase 1 (IDH1). Interestingly, their increased expression was mostly dependent on RTG2. Impaired respiratory competence in the HAP4 mutant does not affect its faster adaptive response to stress. These findings indicate that the involvement of the RTG pathway in osmostress is fostered in a cellular context of constitutively reduced respiratory capacity. Moreover, it is evident that the RTG pathway mediates peroxisomes–mitochondria communication by modulating the metabolic function of mitochondria in osmoadaptation.
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Interactions between mitochondria and peroxisomes were revealed in studies of the HOG-dependent response to hyperosmotic stress in S. cerevisiae that also involves the Rtg pathway.
“Interactions between mitochondria and peroxisomes were revealed in the studies of HOG-dependent response to the hyperosmotic stress in S. cerevisiae that also involves the Rtg pathway (Guaragnella et al. 2021; Di Noia et al. 2023).”
From Mitochondrial retrograde control of transcription evolves with respiratory stress, metabolic adaptation, and virulence in budding yeasts (2026) · cites this paper as Di Noia et al. 2023
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- Authors
- Di Noia, M. A., Scarcia, P., Agrimi, G., Ocheja, O. B., Wahid, E., Pisano, I., Paradies, E., Palmieri, L., Guaragnella, C., & Guaragnella, N.
- Affiliations
- Department of Biosciences, Biotechnologies and Environment, University of Bari “Aldo Moro”, 70125 Bari, Italy
- University of Bari Aldo Moro (IT)
- Polytechnic University of Bari (IT)
- Institute of Biomembranes, Bioenergetics and Molecular Biotechnologies (IT)
- Corresponding author
- Guaragnella, Nicoletta
- ORCID
- Venue
- International Journal of Molecular Sciences
- Publisher
- MDPI AG
- Published
- 2023-03-10
- Volume
- 24
- Issue
- 6
- Pages
- 5320
- ISSN
- 1422-0067 (ISSN-L)
- PMC
- PMC10049445
- OpenAlex
- W4324094618
- Cited by
- 17
- References
- 31
- Citations by year
- 2026: 5 · 2025: 5 · 2024: 6 · 2023: 1
- FWCI
- 1.50
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- International Journal of Molecular Sciences (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- CINECA IRIS Institutional Research Information System (University of Bari Aldo Moro) (submittedVersion, cc-by)
- Funders
- Piano Stralcio “Ricerca e innovazione 2015–2017” del Fondo per lo Sviluppo e la Coesione. Anno Accademico 2020/2021—Ciclo XXXVI” (D.D. 1233/2020, 2020RRJPSL_001, 2017PAB8EM_005)
- BioSense-Biosensors for IoT-based Precision Farming (D.D. 1233/2020, 2020RRJPSL_001, 2017PAB8EM_005)
- Ministry of University and Research, Progetti di Ricerca Nazionale (PRIN) (D.D. 1233/2020, 2020RRJPSL_001, 2017PAB8EM_005)
- Biochemical mechanisms and cellular consequences of mitochondrial cation flux: from bioenergetics to metabolic rewiring (D.D. 1233/2020, 2020RRJPSL_001, 2017PAB8EM_005)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fungal and yeast genetics research
- Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
- Keywords
- HAP4, retrograde signaling, osmoadaptation, osmotic stress, mitochondrial respiration, Saccharomyces cerevisiae, salt stress, IDH1
- MeSH terms
- Citrate (si)-Synthase, Citric Acid Cycle, Saccharomyces cerevisiae, Signal Transduction, Gene Expression Regulation, Fungal, Saccharomyces cerevisiae Proteins
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