A brain-enriched Drp1 isoform associates with lysosomes, late endosomes, and the plasma membrane.
J Biol Chem
; 293(30): 11809-11822, 2018 07 27.
Article
in En
| MEDLINE
| ID: mdl-29853636
ABSTRACT
Dynamin-related protein 1 (Drp1) constricts mitochondria as a mechanochemical GTPase during mitochondrial division. The Drp1 gene contains several alternative exons and produces multiple isoforms through RNA splicing. Here we performed a systematic analysis of Drp1 transcripts in different mouse tissues and identified a previously uncharacterized isoform that is highly enriched in the brain. This Drp1 isoform is termed Drp1ABCD because it contains four alterative exons A, B, C, and D. Remarkably, Drp1ABCD is located at lysosomes, late endosomes, and the plasma membrane in addition to mitochondria. Furthermore, Drp1ABCD is concentrated at the interorganelle interface between mitochondria and lysosomes/late endosomes. The localizations of Drp1ABCD at lysosomes, late endosomes, and the plasma membrane require two exons, A and B, that are present in the GTPase domain. Drp1ABCD assembles onto these membranes in a manner that is regulated by its oligomerization and GTP hydrolysis. Experiments using lysosomal inhibitors show that the association of Drp1ABCD with lysosomes/late endosomes depends on lysosomal pH but not their protease activities. Thus, Drp1 may connect mitochondria to endosomal-lysosomal pathways in addition to mitochondrial division.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Endosomes
/
Brain
/
Cell Membrane
/
Dynamins
/
Lysosomes
Type of study:
Risk_factors_studies
Limits:
Animals
Language:
En
Journal:
J Biol Chem
Year:
2018
Type:
Article