Ribosomal Protein uL11 as a Regulator of Metabolic Circuits Related to Aging and Cell Cycle.

Mateusz Mołoń,Przemysław Grela,Monika Kula-Maximenko,Eliza Molestak,Marek Tchórzewski

doi:10.3390/cells9071745

Abstract

Aging is a biological phenomenon common to all living organisms. It is thought that the rate of aging is influenced by diverse factors, in many cases related to the control of energy metabolism, i.e., the so-called pro-longevity effects of starvation. Translation, regarded as the main energy consumption process, lies at the center of interest, as it has a significant impact on the longevity phenomenon. It has been shown that perturbations in the translational apparatus may lead to a lower rate of aging. Therefore, the main aim of this study was to investigate aging in relation to the protein biosynthesis circuit, taking into account the uL11 ribosomal protein as a vital ribosomal element. To this end, we used set of yeast mutants with deleted single uL11A or uL11B genes and a double disruptant uL11AB mutant. We applied an integrated approach analyzing a broad range of biological parameters of yeast mutant cells, especially the longevity phenomenon, supplemented with biochemical and high throughput transcriptomic and metobolomic approaches. The analysis showed that the longevity phenomenon is not fully related to the commonly considered energy restriction effect, thus the slow-down of translation does not represent the sole source of aging. Additionally, we showed that uL11 can be classified as a moonlighting protein with extra-ribosomal function having cell-cycle regulatory potential.

Highlights

Aging is a universal biological process that may be generally defined as multifactorial events associated with functional deterioration of physiological and biochemical parameters, strictly dependent on time, which leads to cell death
To obtain insight into the role of the translational machinery in aging, we used S. cerevisiae as a model system, and the uL11 ribosomal protein was taken into consideration as an experimental object
Despite the secondary role of r-proteins in the ribosome action, they assist the ribosome in translation from the qualitative and quantitative points of view, contributing significantly to the overall performance of the translational machinery [15,16]

Summary

Introduction

Aging is a universal biological process that may be generally defined as multifactorial events associated with functional deterioration of physiological and biochemical parameters, strictly dependent on time, which leads to cell death. According to prevailing opinions, aging may occur either as a result of a purposeful program driven by a web of interconnected controlled events or as stochastic, random, and accidental events leading to a metabolic decline [1]. Aging research has been focused on several experimental systems, e.g., yeast [2], nematode [3], fruit fly [4], and mouse or rat models [5], indicating that the energy consumption balance is the main issue. It has been shown that the rate of aging is strongly influenced by diverse factors. Translation, which is an energetically demanding process, is strictly related to modulation of the aging phenomenon: when the protein synthesis declines, the organismal

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