To date, we understand a great deal about the signaling pathways and mechanisms that maintain cellular health during amino acid limitation ( Efeyan et al., 2015 Rabinowitz and White, 2010). As with all nutrients, cells must tightly regulate amino acid levels by coordinating the rates of amino acid uptake, utilization and storage. Additionally, cells also modulate mitochondrial function, dynamics, and transport in response to numerous nutrient cues to maintain metabolic homeostasis during nutrient excess and caloric restriction ( Liesa and Shirihai, 2013).Īmong metabolic perturbations faced by cells, intracellular amino acid excess is a common defect in nutrient homeostasis that can alter mitochondrial function ( Braun et al., 2015 Hughes et al., 2020 Li et al., 2017 Sun et al., 2016) and is associated with diabetes ( Knebel et al., 2016 Newgard et al., 2009 Ruiz-Canela et al., 2018 Wang et al., 2011 Xu et al., 2013), cardio-vascular disease ( Shah et al., 2010 Würtz et al., 2015) and a host of inborn errors of metabolism ( Aliu et al., 2018). These quality control mechanisms include internal mitochondrial proteases that regulate turnover of proteins localized to the mitochondrial matrix, the inner membrane (IM), and the intermembrane space (IMS) ( Quirós et al., 2015) the ubiquitin proteasome system, which controls clearance of proteins at the mitochondrial outer membrane (OM) ( Karbowski and Youle, 2011) the mitochondrial unfolded protein response, which responds to protein aggregation stress within mitochondria ( Shpilka and Haynes, 2018) mitochondrial fusion and fission, which integrate numerous signaling pathways to maintain balance of the mitochondrial network ( Youle and van der Bliek, 2012) mitophagy, which promotes selective elimination of damaged mitochondria via Parkin-dependent and −independent autophagy ( Pickles et al., 2018) and mitochondrial-derived vesicles (MDVs), which target damaged mitochondrial proteins from all sub-mitochondrial compartments for lysosomal degradation via small, sub-micron sized vesicles (70 – 150nm) in response to oxidative insults ( Sugiura et al., 2014). Cells utilize several systems to monitor, maintain and adjust mitochondrial function in response to various cellular stresses including protein aggregation, increased reactive oxygen species (ROS) formation, and loss of the mitochondrial membrane potential (ΔΨ) ( Barbour and Turner, 2014). Mitochondria are double membrane-bound organelles that play essential roles in cellular energy production, amino acid homeostasis, and lipid metabolism, and their functional decline is associated with numerous age-related and metabolic disorders ( Nunnari and Suomalainen, 2012). Thus, MDCs represent an evolutionarily conserved nutrient-responsive mitochondrial remodeling system. Mammalian MDCs are responsive to changes in amino acid levels during translation inhibition, and are not activated by other common cellular stressors. These compartments are enriched for the carrier receptor Tomm70A and other select mitochondrial outer and inner membrane cargo, associate with the ER membrane, and require the conserved GTPase Miro1 for formation. Specifically, we find that inhibition of protein translation stimulates formation of dynamic, micron-sized compartments that associate with the mitochondrial network. Here, we show that MDCs are conserved in mammals, and like their yeast counterparts, are responsive to the intracellular amino acid content. While emerging evidence supports an important function for MDCs in protecting cells from metabolic stress, whether this system exists beyond yeast remains unclear. It does not store any personal data.We recently identified a new cellular structure in yeast, called the Mitochondrial-Derived Compartment (MDC), that forms on mitochondria in response to amino acid excess. The cookie is set by the GDPR Cookie Consent plugin and is used to store whether or not user has consented to the use of cookies. The cookie is used to store the user consent for the cookies in the category "Performance". This cookie is set by GDPR Cookie Consent plugin. The cookie is used to store the user consent for the cookies in the category "Other. The cookies is used to store the user consent for the cookies in the category "Necessary". The cookie is set by GDPR cookie consent to record the user consent for the cookies in the category "Functional". The cookie is used to store the user consent for the cookies in the category "Analytics". These cookies ensure basic functionalities and security features of the website, anonymously. Necessary cookies are absolutely essential for the website to function properly.