Divergent branches of mitochondrial signaling regulate specific genes and the viability of specialized cell types of differentiated yeast colonies

// Kristýna Podholova 1,* , Vitězslav Plocek 1,* , Stanislava Resetarova 2 , Helena Kucerova 1,2 , Otakar Hlavacek 2 , Libuse Vachova 2 and Zdena Palkova 1 1 Department of Genetics and Microbiology, Faculty of Science, Charles University in Prague, Prague, Czech Republic 2 Institute of Microbiology of the CAS, v.v.i., Prague, Czech Republic * The authors have contributed equally to this paper Correspondence to: Zdena Palkova, email: // Keywords : mitochondrial retrograde signaling, development and differentiation, ageing and longevity Received : October 05, 2015 Accepted : February 23, 2016 Published : March 15, 2016 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.