Mitochondrial Retrograde Signaling Contributes to Metabolic Differentiation in Yeast Colonies.

Vítězslav Plocek,Alexandra Pokorná,Kristýna Fadrhonc,Jana Maršíková,Otakar Hlaváček,Derek Wilkinson,Zdena Palková,Libuše Váchová

doi:10.3390/ijms22115597

Vítězslav Plocek, Alexandra Pokorná + Show 6 more

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https://doi.org/10.3390/ijms22115597

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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.

Highlights

Accepted: 21 May 2021Mitochondria in eukaryotic cells provide key metabolic processes, energy production, cellular redox state, and a number of signaling processes affecting overall cell physiology.Disorders in various mitochondrial metabolic and signaling processes often lead to severe disorders in mammals [1]
Whether caused by mitochondrial damage or changes in the conditions to which the cell is exposed, can activate cellular responses by a mechanism called “mitochondrial retrograde signaling”, where changes in mitochondria cause extensive changes in nuclear gene expression to help the cell adapt to the new conditions [2]
Previous findings indicate the importance of mitochondria and the RTG pathway in the development and differentiation of yeast colonies [12,13,14,17]

Summary

Introduction

Accepted: 21 May 2021Mitochondria in eukaryotic cells provide key metabolic processes, energy production, cellular redox state, and a number of signaling processes affecting overall cell physiology.Disorders in various mitochondrial metabolic and signaling processes often lead to severe disorders in mammals [1]. Whether caused by mitochondrial damage or changes in the conditions to which the cell is exposed, can activate cellular responses by a mechanism called “mitochondrial retrograde signaling”, where changes in mitochondria cause extensive changes in nuclear gene expression to help the cell adapt to the new conditions [2]. Molecular mechanisms of retrograde signaling in mammals are poorly understood, but such signaling is often associated with changes, typical of cancer disorders, including activation of enzymes involved in aerobic glycolysis [1]. The most studied system of retrograde signaling (the RTG pathway) in yeast Saccharomyces cerevisiae includes activators—a heterodimeric transcription factor composed of the Rtg1p and Rtg3p proteins and the Rtg2p protein, which registers mitochondrial signal(s) by an unknown mechanism [3].

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