Fundamental limits to progression of cellular life in frigid environments

Abstract

Life on Earth, including for microbes and cold-blooded animals, often occurs in frigid environments. At frigid temperatures, nearly all intracellular processes slow down which is colloquially said to decelerate lifes pace and, potentially, aging. But even for one cell, an outstanding conceptual challenge is rigorously explaining how the slowed-down intracellular processes collectively sustain a cells life and set its pace. Here, by monitoring individual yeast cells for months at near-freezing temperatures, we show how global gene-expression dynamics and Reactive Oxygen Species (ROS) act together as the primary factors that dictate and constrain the pace at which a budding yeasts life can progresses in frigid environments. We discovered that yeast cells help each other in surviving and dividing at frigid temperatures. By investigating the underlying mechanism, involving glutathione secretion, we discovered that ROS is the primary determinant of yeasts ability to survive and divide at near-freezing temperatures. Observing days-to-months-long cell-cycle progression in individual cells revealed that ROS inhibits S-G2-M (replicative) phase while elongating G1 (growth) phase up to a temperature-dependent threshold duration, beyond which yeast cannot divide and bursts as an unsustainably large cell. We discovered that an interplay between global gene-expression speed and ROS sets the threshold G1-duration by measuring rates of genome-wide transcription and protein synthesis at frigid temperatures and then incorporating them into a mathematical model. The same interplay yields unbeatable "speed limits" for cell cycling - shortest and longest allowed doubling times - at each temperature. These results establish quantitative principles for engineering cold-tolerant microbes and reveal how frigid temperatures can fundamentally constrain microbial life and cell cycle at the systems-level.