title: Divergent branches of mitochondrial signaling regulate specific genes and the viability of specialized cell types of differentiated yeast colonies.
abstract: Mitochondrial retrograde signaling mediates communication from altered mitochondria to the nucleus and is involved in many normal and pathophysiological changes, including cell metabolic reprogramming linked to cancer development and progression in mammals. The major mitochondrial retrograde pathway described in yeast includes three activators, Rtg1p, Rtg2p and Rtg3p, and repressors, Mks1p and Bmh1p/Bmh2p. Using differentiated yeast colonies, we show that Mks1p-Rtg pathway regulation is complex and includes three branches that divergently regulate the properties and fate of three specifically localized cell subpopulations via signals from differently altered mitochondria. The newly identified RTG pathway-regulated genes ATO1/ATO2 are expressed in colonial upper (U) cells, the cells with active TORC1 that metabolically resemble tumor cells, while CIT2 is a typical target induced in one subpopulation of starving lower (L) cells. The viability of the second L cell subpopulation is strictly dependent on RTG signaling. Additional co-activators of Rtg1p-Rtg3p specific to particular gene targets of each branch are required to regulate cell differentiation.
authors.affiliation: Department of Genetics and Microbiology, Faculty of Science, Charles University in Prague, Prague, Czech Republic.
authors.forename: Kristýna
authors.initials: K
authors.lastname: Podholová
authors.affiliation: Department of Genetics and Microbiology, Faculty of Science, Charles University in Prague, Prague, Czech Republic.
authors.forename: Vítězslav
authors.initials: V
authors.lastname: Plocek
authors.affiliation: Institute of Microbiology of the CAS, v.v.i., Prague, Czech Republic.
authors.forename: Stanislava
authors.initials: S
authors.lastname: Rešetárová
authors.affiliation: Department of Genetics and Microbiology, Faculty of Science, Charles University in Prague, Prague, Czech Republic.|Institute of Microbiology of the CAS, v.v.i., Prague, Czech Republic.
authors.forename: Helena
authors.initials: H
authors.lastname: Kučerová
authors.affiliation: Institute of Microbiology of the CAS, v.v.i., Prague, Czech Republic.
authors.forename: Otakar
authors.initials: O
authors.lastname: Hlaváček
authors.affiliation: Institute of Microbiology of the CAS, v.v.i., Prague, Czech Republic.
authors.forename: Libuše
authors.initials: L
authors.lastname: Váchová
authors.affiliation: Department of Genetics and Microbiology, Faculty of Science, Charles University in Prague, Prague, Czech Republic.
authors.forename: Zdena
authors.initials: Z
authors.lastname: Palková
mesh_terms: D002454:Cell Differentiation / Q000502:physiology; D002470:Cell Survival / Q000502:physiology*; D005800:Genes, Fungal / Q000502:physiology; D008928:Mitochondria / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000502:physiology*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*
chemical_list: D029701:Saccharomyces cerevisiae Proteins
keywords: ageing and longevity; development and differentiation; mitochondrial retrograde signaling