RT Journal Article
SR Electronic
T1 Microtubule-dependent and independent roles of spastin in lipid droplet dispersion and biogenesis
JF Life Science Alliance
JO Life Sci. Alliance
FD Life Science Alliance LLC
SP e202000715
DO 10.26508/lsa.202000715
VO 3
IS 6
A1 Nimesha Tadepalle
A1 Lennart Robers
A1 Matteo Veronese
A1 Peter Zentis
A1 Felix Babatz
A1 Susanne Brodesser
A1 Anja V Gruszczyk
A1 Astrid Schauss
A1 Stefan Höning
A1 Elena I Rugarli
YR 2020
UL https://www.life-science-alliance.org/content/3/6/e202000715.abstract
AB Lipid droplets (LDs) are metabolic organelles that store neutral lipids and dynamically respond to changes in energy availability by accumulating or mobilizing triacylglycerols (TAGs). How the plastic behavior of LDs is regulated is poorly understood. Hereditary spastic paraplegia is a central motor axonopathy predominantly caused by mutations in SPAST, encoding the microtubule-severing protein spastin. The spastin-M1 isoform localizes to nascent LDs in mammalian cells; however, the mechanistic significance of this targeting is not fully explained. Here, we show that tightly controlled levels of spastin-M1 are required to inhibit LD biogenesis and TAG accumulation. Spastin-M1 maintains the morphogenesis of the ER when TAG synthesis is prevented, independent from microtubule binding. Moreover, spastin plays a microtubule-dependent role in mediating the dispersion of LDs from the ER upon glucose starvation. Our results reveal a dual role of spastin to shape ER tubules and to regulate LD movement along microtubules, opening new perspectives for the pathogenesis of hereditary spastic paraplegia.