Genetic Screen Uncovers a Dual Role for Phospholipids in Mitochondrial-Derived Compartment Biogenesis
Year: 2023
Type: preprint
Abstract: ABSTRACT Cells utilize multiple mechanisms to maintain mitochondrial homeostasis in response to stress. We recently identified a cellular structure, called the mitochondria-derived compartment (MDC), that is generated from mitochondria in response to amino acid overabundance. MDCs selectively sequester proteins from mitochondria for subsequent degradation, and loss of MDCs sensitizes cells to amino acid stress. Here, we conducted a microscopy-based screen in budding yeast to identify factors that regulate MDC formation. We found that levels of two mitochondrial phospholipids, cardiolipin (CL) and phosphatidylethanolamine (PE), regulate MDC biogenesis in opposing directions. CL depletion impairs MDC biogenesis, whereas PE reduction leads to constitutive MDC formation. Additionally, in response to MDC-inducing agents, cellular and mitochondrial PE declines in an amino acid-dependent manner. Overexpressing mitochondrial PE synthesis pathway components suppresses MDC biogenesis during amino acid stress. Altogether, our data indicate a requirement for CL in MDC biogenesis, and suggest that PE depletion may serve as a regulatory signal for MDC formation downstream of MDC-inducing metabolic stress. SUMMARY Xiao et al. identify distinct roles for the phospholipids cardiolipin and phosphatidylethanolamine in mitochondria-derived compartment (MDC) biogenesis. They show that cardiolipin is required for MDC formation, whereas a decline in phosphatidylethanolamine in response to amino acid stress triggers MDC biogenesis.
Institution: University of Utah
Language: English
Subfield: Epidemiology
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W4321331223