New Ca(2+)-dependent regulators of autophagosome maturation.
Autophagy is a membrane trafficking pathway responsible for the breakdown of unwanted intracellular materials and crucial for the cell healthiness and survival. In the autophagic flux, various dynamic membrane rearrangements occurs starting with the elongation of the phagophore and its closure to build an autophagosome and ending with its fusion with late endosomes and lysosomes to form an autolysosome. Although Ca(2+) is a well established regulator of membrane fusion events, little is known about its role in these processes during autophagy. Recent studies, based on proteomic analyses of lysosomal membranes, have provided new insights into this field of study. Thus, the levels on lysosomal membranes of annexin A1, annexin A5 and copine 1, three proteins that bind to phospholipid membranes in a Ca(2+)-dependent manner, increased under nutrient deprivation, a condition that promotes autophagic degradation. In addition, two different studies showed that annexin A5 and annexin A1 are involved in autophagosome maturation. Here, we discuss the molecular mechanisms by which the fusion of autophagosomes with endosomes and lysosomes could be regulated by these three proteins and Ca(2+).
Laboratorio de Biología Celular; Centro de Investigación Príncipe; Valencia, Spain.
Ghita
G
Ghislat
Erwin
E
Knecht