Mitochondrial-nuclear heme trafficking in budding yeast is regulated by GTPases that control mitochondrial dynamics and ER contact sites

Osiris Martinez-Guzman, Mathilda M. Willoughby, Arushi Saini, Jonathan V. Dietz, Iryna Bohovych, Amy E. Medlock, Oleh Khalimonchuk, Amit R. Reddi

Research output: Contribution to journalArticle

Abstract

Heme is a cofactor and signaling molecule that is essential for much of aerobic life. All heme-dependent processes in eukaryotes require that heme is trafficked from its site of synthesis in the mitochondria to hemoproteins located throughout the cell. However, the mechanisms governing the mobilization of heme out of the mitochondria, and the spatiotemporal dynamics of these processes, are poorly understood. Here, using genetically encoded fluorescent heme sensors, we developed a live-cell assay to monitor heme distribution dynamics between the mitochondrial inner membrane, where heme is synthesized, and the mitochondrial matrix, cytosol and nucleus. Surprisingly, heme trafficking to the nucleus is ∼25% faster than to the cytosol or mitochondrial matrix, which have nearly identical heme trafficking dynamics, potentially supporting a role for heme as a mitochondrial-nuclear retrograde signal. Moreover, we discovered that the heme synthetic enzyme 5-aminolevulinic acid synthase (ALAS, also known as Hem1 in yeast), and GTPases in control of the mitochondrial dynamics machinery (Mgm1 and Dnm1) and ER contact sites (Gem1), regulate the flow of heme between the mitochondria and nucleus. Overall, our results indicate that there are parallel pathways for the distribution of bioavailable heme.

Original languageEnglish (US)
Article number237917
JournalJournal of cell science
Volume133
Issue number10
DOIs
StatePublished - May 2020

Keywords

  • Heme
  • Heme transport
  • Mitochondrial dynamics
  • Yeast

ASJC Scopus subject areas

  • Cell Biology

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    Martinez-Guzman, O., Willoughby, M. M., Saini, A., Dietz, J. V., Bohovych, I., Medlock, A. E., Khalimonchuk, O., & Reddi, A. R. (2020). Mitochondrial-nuclear heme trafficking in budding yeast is regulated by GTPases that control mitochondrial dynamics and ER contact sites. Journal of cell science, 133(10), [237917]. https://doi.org/10.1242/jcs.237917