biostudies-literatureHanna DANIEHS NIH HHSNational Science Foundation (NSF)NIGMS NIH HHSGeorgia Institute of Technology (Georgia Tech)HHS | NIH | National Institute of General Medical Sciences (NIGMS)HHS | NIH | National Institute of Environmental Health Sciences (NIEHS)12378-12393https://www.ebi.ac.uk/biostudies/studies/S-EPMC6093230biostudies-literatureUnknown293(32)Protoheme (hereafter referred to as heme) is an essential cellular cofactor and signaling molecule that is also potentially cytotoxic. To mitigate heme toxicity, heme synthesis and degradation are tightly coupled to heme utilization in order to limit the intracellular concentration of "free" heme. Such a model, however, would suggest that a readily accessible steady-state, bioavailable labile heme (LH) pool is not required for supporting heme-dependent processes. Using the yeast <i>Saccharomyces cerevisiae</i> as a model and fluorescent heme sensors, site-specific heme chelators, and molecular genetic approaches, we found here that 1) yeast cells preferentially use LH in heme-depleted conditions; 2) sequestration of cytosolic LH suppresses heme signaling; and 3) lead (Pb²⁺) streThe Journal of biological chemistryHeme bioavailability and signaling in response to stress in yeast cells.PMC6093230R01 GM118744ES025661R33 ES025661GM118744start-upR21 ES025661MCB-1552791Reddi ARTorres MPHanna DAKim HMartinez-Guzman OHu RfalseHeme bioavailability and signaling in response to stress in yeast cells.Protoheme (hereafter referred to as heme) is an essential cellular cofactor and signaling molecule that is also potentially cytotoxic. To mitigate heme toxicity, heme synthesis and degradation are tightly coupled to heme utilization in order to limit the intracellular concentration of "free" heme. Such a model, however, would suggest that a readily accessible steady-state, bioavailable labile heme (LH) pool is not required for supporting heme-dependent processes. Using the yeast <i>Saccharomyces cerevisiae</i> as a model and fluorescent heme sensors, site-specific heme chelators, and molecular genetic approaches, we found here that 1) yeast cells preferentially use LH in heme-depleted conditions; 2) sequestration of cytosolic LH suppresses heme signaling; and 3) lead (Pb²⁺) stre2018-01-01T00:00:00Z2018 Aug2026-04-29T02:45:39.011Z2019-08-13T07:01:30ZS-EPMC60932302992158510.1074/jbc.RA118.00212510.1074/jbc.ra118.002125