Abstract
In all eukaryotic cells, intracellular organization and spatial separation of incompatible biochemical processes is established by individual cellular subcompartments in form of membrane-bound organelles. Virtually all of these organelles are physically connected via membrane contact sites (MCS), allowing interorganellar communication and a functional integration of cellular processes. These MCS coordinate the exchange of diverse metabolites and serve as hubs for lipid synthesis and trafficking. While this of course indirectly impacts on a plethora of biological functions, including autophagy, accumulating evidence shows that MCS can also directly regulate autophagic processes. Here, we focus on the nexus between interorganellar contacts and autophagy in yeast and mammalian cells, highlighting similarities and differences. We discuss MCS connecting the ER to mitochondria or the plasma membrane, crucial for early steps of both selective and non-selective autophagy, the yeast-specific nuclear–vacuolar tethering system and its role in microautophagy, the emerging function of distinct autophagy-related proteins in organellar tethering as well as novel MCS transiently emanating from the growing phagophore and mature autophagosome.
Highlights
Intracellular compartmentalization in form of membrane-bound organelles represents a defining feature of eukaryotic cells
The identification of contact sites between the growing phagophore and the endoplasmic reticulum (ER) established by distinct autophagy-related (Atg) proteins, a role for mitochondria-associated membranes (MAMs) and their associated proteins in autophagosome biogenesis, as well as interactions between crucial regulators of autophagy and membrane contact sites (MCS) tether proteins highlight the importance of organellar connectivity in form of physical contact for autophagy
Physical contact between the ER and mitochondria established by MAMs in mammalian cells and ER–mitochondria encounter structure (ERMES) in yeast is central for various autophagic processes, in particular for mitophagy
Summary
Intracellular compartmentalization in form of membrane-bound organelles represents a defining feature of eukaryotic cells. 9, x FOR PEER REVIEW of 22 years [4,5], a large number of heterotypic MCS involve the endoplasmic reticulum (ER) [6,7], cellular metabolism and homeostasis. MCS play decisive role regulating thehigher breakdown of in Accumulating regulating the evidence breakdown of cellular viaa autophagy in in both yeast and eukaryotic cellular material autophagy in both yeast and higher eukaryotic organisms. Cargo is sequestered into a double-membraned vesicle termed termed autophagosome, which subsequently with the or lysosome orcounterpart, the yeast counterpart, the autophagosome, which subsequently fuses withfuses the lysosome the yeast the vacuole [26]. We focus on the emerging nexus between MCS various subtypes of autophagy in bothMCS baker’s yeast and mammals, highlighting similarities and weand focus on the emerging nexus between and various subtypes of autophagy in both baker’s differences betweenhighlighting these species.similarities and differences between these species
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