ArticleThe Journal of biological chemistry2020
"Labile" heme critically regulates mitochondrial biogenesis through the transcriptional co-activator Hap4p in
Article in The Journal of biological chemistry, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed, 15 citations in OpenAlex.
- Regional and Systemic Metabolic Remodeling Promotes Longevity by Bioengineered Yeast-Derived Lipids.bioRxiv : the preprint server for biology · 2026Article
- Review
- A high copy suppressor screen identifies factors enhancing the allotopic production of subunit II of cytochrome c oxidase.G3 (Bethesda, Md.) · 2025Article
- Iron Homeostatic Regulation in Saccharomyces cerevisiae: Introduction to a Computational Modeling Method.Methods in molecular biology (Clifton, N.J.) · 2024Review
- Inactivation ofInternational journal of molecular sciences · 2023Article
- Ubiquitin-Conjugating Enzymes Ubc1 and Ubc4 Mediate the Turnover of Hap4, a Master Regulator of Mitochondrial Biogenesis inMicroorganisms · 2022Article
- Mössbauer-based molecular-level decomposition of the Saccharomyces cerevisiae ironome, and preliminary characterization of isolated nuclei.Metallomics : integrated biometal science · 2022Article
- Yap5 Competes With Hap4 for the Regulation of Iron Homeostasis Genes in the Human PathogenFrontiers in cellular and infection microbiology · 2021Article
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Heme (iron protoporphyrin IX) is a well-known prosthetic group for enzymes involved in metabolic pathways such as oxygen transport and electron transfer through the mitochondrial respiratory chain. However, heme has also been shown to be an important regulatory molecule (as "labile" heme) for diverse processes such as translation, kinase activity, and transcription in mammals, yeast, and bacteria. Taking advantage of a yeast strain deficient for heme production that enabled controlled modulation and monitoring of labile heme levels, here we investigated the role of labile heme in the regulation of mitochondrial biogenesis. This process is regulated by the HAP complex in yeast. Using several biochemical assays along with EM and epifluorescence microscopy, to the best of our knowledge, we show for the first time that cellular labile heme is critical for the post-translational regulation of HAP complex activity, most likely through the stability of the transcriptional co-activator Hap4p. Consequently, we found that labile heme regulates mitochondrial biogenesis and cell growth. The findings of our work highlight a new mechanism in the regulation of mitochondrial biogenesis by cellular metabolites.
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