Mitochondrial Retrograde Signaling Contributes to Metabolic Differentiation in Yeast Colonies

Abstract

During development of yeast colonies, various cell subpopulations form, which differ in their properties and specifically localize within the structure. Three branches of mitochondrial retrograde (RTG) signaling play a role in colony development and differentiation, each of them activating the production of specific markers in different cell types. Here, aiming to identify proteins and processes controlled by the RTG pathway, we analyzed proteomes of individual cell subpopulations from colonies of strains, mutated in genes of the RTG pathway. Resulting data, along with microscopic analyses revealed that the RTG pathway predominantly regulates processes in U cells, long-lived cells with unique properties, which are localized in upper colony regions. Rtg proteins therein activate processes leading to amino acid biosynthesis, including transport of metabolic intermediates between compartments, but also repress expression of mitochondrial ribosome components, thus possibly contributing to reduced mitochondrial translation in U cells. The results reveal the RTG pathway’s role in activating metabolic processes, important in U cell adaptation to altered nutritional conditions. They also point to the important role of Rtg regulators in repressing mitochondrial activity in U cells.

Spatially structured yeast communities: Understanding structure formation and regulation with omics tools

“…Many of the metabolic (transcriptional) features in these cells correlate with the transcriptional changes identified in the entire colony population during the transition from acidic to alkaline phase [20] . Many activations of expression in U cells are evident at both the transcriptome and proteome levels [5] , [6] , [22] , [23] , as is the most pronounced repressive feature - decreased expression (mRNA and protein) of mitochondrial respiratory chain components, resulting in decreased mitochondrial OxPhos activity and respiratory shutdown. This change was also observed during colony switching between phases and appears to contribute to stress reduction in U cells.…”

“…This change was also observed during colony switching between phases and appears to contribute to stress reduction in U cells. Subsequently, several branches of the mitochondria-driven retrograde signaling pathway have been identified to regulate the expression of specific targets in differentiated colony subpopulations [9] , [22] . In contrast to U cells, L cells have the characteristics of starving, stressed cells, but lack some typical features of stress-adapted cells (such as accumulation of storage compounds and a strong cell wall), and partially resemble colony cells from “acidic” phase before differentiation [5] , [23] .…”

“…B, cross sections of the structures visualized by 2-photon confocal microscopy (colony and colony biofilm) or wide-field microscopy (biofilm). Colonies: green, U-layer of cells expressing Cit3p-GFP; red, L-cells visualized as cell autofluorescence (adapted from [22] ); colony biofilm: Rpa19p-GFP level differs in aerial and root parts (adapted from [7] ); vertical structure of SLI biofilm (adapted from [30] ). Dashed lines, surface of agar (white), polystyrene surface (black).…”

Alleviating glucose repression and enhancing respiratory capacity to increase itaconic acid production

“…Activating the gene expressions of the TCA cycle and oxidative phosphorylation by regulating glucose-sensing signaling pathways could be an effective solution to improve ATP supply. Mitochondrial retrograde signaling (RTG signaling) responds to changes in intracellular energy and glutamic acid auxotrophy, and removing glucose repression of this signaling will up-regulate the expression of genes in the TCA cycle [ 15 , 16 ]. By the way, most genes of the IA synthesis pathway are controlled by RTG signaling.…”

Mitochondrial Research: Yeast and Human Cells as Models

“…Changes in mitochondrial functionality trigger a mechanism known as “mitochondrial retrograde signalling”, by which cells respond and adapt to said mitochondrial dysfunction by extensive changes in nuclear gene expression [ 9 , 10 ]. Retrograde (RTG) signalling is known to be involved in the development and differentiation of yeast colonies, as reported by the group of Palková [ 11 ], which further analysed proteomes of cell subpopulations: U cells and L cells in the upper and lower colony regions, respectively [ 12 ]. Rtg proteins were shown to regulate different metabolic processes, predominantly in U cells, which is important in their adaptation to changes in nutritional conditions.…”