Several cellular processes depend on the synthesis of haem b at the mitochondrial inner membrane and its distribution across the cell. It was thought that haem trafficking was a sequential process, starting with its direct export to the cytosol before reaching other compartments. Recently, alternative distribution mechanisms involving mitochondria and their contact sites with the endoplasmic reticulum (ER) have been considered. In their study, Osiris Martinez-Guzman and colleagues in the lab of Amit Reddi (Martinez-Guzman et al., 2020) analyse the spatio-temporal dynamics of intracellular haem trafficking that occurs simultaneously to the mitochondrial matrix, cytosol and nucleus of budding yeast, using genetically encoded fluorescent haem sensors. Surprisingly, they note that the rate of transport to the nucleus is 25% faster than the rate of transport to the mitochondrial matrix or the cytosol, suggesting a possible role for haem in mitochondrial–nuclear retrograde signalling. GTPases that are responsible for the regulation of mitochondrial dynamics, such as Dnm1 and Mgm1, and of mitochondrial–ER contact sites, such as Gem1, influence haem nuclear transfer. Moreover, 5-aminolevulinic acid synthase (ALAS, encoded by hem1 in yeast), which is involved the first step of haem synthesis, also regulates nuclear haem transport. This study thus reveals a new pathway of haem trafficking to the nucleus via ER–mitochondria contact sites and demonstrates the close integration between haem synthesis and trafficking.
- © 2020. Published by The Company of Biologists Ltd