Amino Acid Homeostasis and Chronological Longevity in Saccharomyces cerevisiae

Abstract

Understanding how non-dividing cells remain viable over long periods of time, which may be decades in humans, is of central importance in understanding mechanisms of aging and longevity. The long-term viability of non-dividing cells, known as chronological longevity, relies on cellular processes that degrade old components and replace them with new ones. Key among these processes is amino acid homeostasis. Amino acid homeostasis requires three principal functions: amino acid uptake, de novo synthesis, and recycling. Autophagy plays a key role in recycling amino acids and other metabolic building blocks, while at the same time removing damaged cellular components such as mitochondria and other organelles. Regulation of amino acid homeostasis and autophagy is accomplished by a complex web of pathways that interact because of the functional overlap at the level of recycling. It is becoming increasingly clear that amino acid homeostasis and autophagy play important roles in chronological longevity in yeast and higher organisms. Our goal in this chapter is to focus on mechanisms and pathways that link amino acid homeostasis, autophagy, and chronological longevity in yeast, and explore their relevance to aging and longevity in higher eukaryotes.

Isp7 Is a Novel Regulator of Amino Acid Uptake in the TOR Signaling Pathway

“…The long-term viability of nondividing cells is also known as chronological longevity (63). Key players that determine chronological longevity are the TOR signaling pathway and amino acid homeostasis (32,64). Our findings suggest a novel link between amino acid uptake and TOR signaling via the 2OG-Fe(II) oxygenase Isp7.…”

Impaired amino acid uptake leads to global metabolic imbalance of Candida albicans biofilms

“…During biofilm maturation, specialized sub-populations differentiate to adapt to stress conditions like nutrient deficiency 31 , 32 . Amino acid homeostasis is critical for cellular growth and maintenance and this process includes three main mechanisms: amino acid uptake, de novo synthesis, and recycling by autophagy 33 . Previous studies showed a link between transcriptional regulation of amino acid utilization genes and C. albicans biofilm formation 15 , 18 – 20 , but the importance of active amino acid uptake and its metabolic consequences have not been addressed.…”

“…Transcriptional down-regulation of energy production was reflected in greatly reduced levels of intracellular metabolites and consequently lower secretion of nitrogenous metabolites into the medium. The low metabolic rate led to the induction of autophagy genes, which is a general response to starvation for various essential nutrients, where cytosolic proteins are targeted to the vacuole for bulk degradation and recycling of amino acids 33 , 40 . Further metabolic compensation was achieved by transcriptional induction of nutrient import, which resembles enhanced transcription of amino acid permease genes in planktonic cells grown under hypoxia 41 .…”

Effect of the Ala234Asp replacement in mitochondrial branched-chain amino acid aminotransferase on the production of BCAAs and fusel alcohols in yeast

“…These findings suggest the presence of unknown regulation mechanisms of BCATs in S. cerevisiae. Attempts have been made to clarify the metabolic regulation in the stationary phase (Zakrajšek et al 2011: Aris et al 2012: Mukai et al 2019. Normally, the fermentation process proceeds over a long period of time-namely, days to weeks.…”