ER-Mitochondria Contacts Promote Mitochondrial-Derived Compartment Biogenesis

Mitochondria are dynamic organelles with essential roles in signaling and metabolism. We recently identified a new cellular structure called the mitochondrial-derived compartment (MDC) that is generated from mitochondria in response to amino acid elevation. MDCs protect cells from amino acid toxicity, but how cells form MDCs is unclear. Here, we show that MDCs are micron-sized, lumen-containing organelles that form at sites of contact between the ER and mitochondria. Upon formation, MDCs stably persist at ER-mitochondria contacts for extended periods of time. MDC formation requires the ER-mitochondria encounter structure (ERMES) and GTP hydrolysis by the conserved GTPase Gem1. Unexpectedly, MDC formation is not linked to the role of ERMES/Gem1 in the maintenance of mitochondrial phospholipid homeostasis. Our results identify an important role for ER-mitochondria contacts in the biogenesis of MDCs. Abbreviations used in this paper: ERMES, ER-mitochondria encounter structure; IMM, inner mitochondrial membrane; MDC, mitochondrial-derived compartment; OMM, outer mitochondrial membrane. Summary English et al. use super-resolution imaging to show that mitochondrial-derived compartments are lumen-containing organelles that form at sites of contact between the ER and mitochondria. Mitochondrial-derived compartment biogenesis requires a noncanonical function of the ERMES complex and the conserved GTPase Gem1.