RT Journal Article
SR Electronic
T1 Mitochondrial-Derived Compartments Facilitate Cellular Adaptation to Amino Acid Stress
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2020.03.13.991091
DO 10.1101/2020.03.13.991091
A1 Max-Hinderk Schuler
A1 Alyssa M. English
A1 Thane J. Campbell
A1 Janet M. Shaw
A1 Adam L. Hughes
YR 2020
UL http://biorxiv.org/content/early/2020/03/14/2020.03.13.991091.abstract
AB Amino acids are essential building blocks of life. However, increasing evidence suggests that elevated amino acids cause cellular toxicity associated with numerous metabolic disorders. How cells cope with elevated amino acids remains poorly understood. Here, we show that a previously identified cellular structure, the mitochondrial-derived compartment (MDC), is a dynamic, lumen-containing organelle that functions to protect cells from amino acid stress. In response to amino acid elevation, MDCs are generated from mitochondria, where they selectively sequester and remove Tom70, a surface receptor required for import of nutrient carriers of the SLC25 family. MDC formation is regulated by levels of mitochondrial carriers, and its activation by amino acids occurs simultaneously with removal of plasma membrane-localized transporters via the multi-vesicular body (MVB) pathway. Combined loss of MDC and MVB formation renders cells sensitive to elevated amino acids, suggesting these pathways operate as a coordinated network to protect cells from amino acid toxicity.