How Membrane Contact Sites Shape the Phagophore

Abstract

During macroautophagy, phagophores establish multiple membrane contact sites (MCSs) with other organelles that are pivotal for proper phagophore assembly and growth. In S. cerevisiae, phagophore contacts have been observed with the vacuole, the ER, and lipid droplets. In situ imaging studies have greatly advanced our understanding of the structure and function of these sites. Here, we discuss how in situ structural methods like cryo-CLEM can give unprecedented insights into MCSs, and how they help to elucidate the structural arrangements of MCSs within cells. We further summarize the current knowledge of the contact sites in autophagy, focusing on autophagosome biogenesis in the model organism S. cerevisiae.

Autophagy as a caretaker of nuclear integrity

“…In contrast, macroautophagy describes the process of cargo sequestration into a de novo synthesized double‐membrane vesicle, called the autophagosome, which subsequently fuses with the lysosome/vacuole [4,5]. During autophagosome biogenesis, transfer of lipids from various intracellular membrane sources facilitates the expansion of an initial flat membrane disk to form a closed autophagosome via a cup‐shaped intermediate, termed the phagophore or isolation membrane [6]. Importantly, macroautophagy and the protein machinery required for autophagosome formation are highly conserved from yeast, where it was originally characterized, to higher eukaryotes such as plants and mammals [7].…”

LC3B is lipidated to large lipid droplets during prolonged starvation for noncanonical autophagy

“…The existence of this pathway suggests that autophagic proteins may serve other purposes beyond autophagosome biology 21 . Interestingly, several autophagy proteins have been identified around lipid droplets (LDs), including Atg2, DFCP1, Atg14L, and possibly LC3 [22][23][24][25][26][27] , implying functional crosstalk between autophagy and LDs that is yet to be fully understood 28 .…”