Journal
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS
Volume 1863, Issue 11, Pages 1423-1432Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.bbalip.2018.08.016
Keywords
Perilipin 5; Perilipin 2; Lipid droplets; Skeletal muscle; Mitochondria; Super-resolution microscopy
Funding
- NanoNextNL, a micro and nanotechnology consortium of the Government of the Netherlands
- EFSD - MSD
- Dutch Diabetes Research Foundation [DF 2014.00.1756]
- NUTRIM School for Nutrition, Toxicology and Metabolism - NWO Graduate Program from Netherlands Organisation for Scientific Research [022.003.011]
- Netherlands Cardiovascular Research Initiative: an initiative with support of the Dutch Heart Foundation [CVON2014-02 ENERGISE]
- Netherlands Organisation for Scientific Research [863.14.003]
Ask authors/readers for more resources
Objective: Intramyocellular lipid droplets (LD) and their coat proteins PLIN2 and PLIN5 are involved in lipolysis, with a putative role for PLIN5 in mitochondrial tethering. Reportedly, these proteins co-localize and cover the surface of the LD. To provide the spatial basis for understanding how these proteins possess their distinct roles, we examined the precise location of PLIN2 and PLIN5 and explored PLIN5 presence at LD-mitochondria contact sites using Stimulated emission depletion (STED) microscopy and correlative light-electron microscopy (CLEM) in human skeletal muscle sections. Methods: LDs were stained by MDH together with combinations of mitochondria] proteins and PLINs. Subcellular distribution and co-localization of PLIN proteins and mitochondria was imaged by STED microscopy (Leica TCS SP8) and quantified using Pearson's correlation coefficients and intensity profile plots. CLEM was employed to examine the presence of PLIN5 on mitochondria-LD contact sites. Results: Both PLIN2 and PLIN5 localized to the LD in a dot-like, juxtaposed fashion rather than colocalizing and covering the entire LD. Both STED and CLEM revealed a high fraction of PLIN5 at the LD-mitochondria interface, but not at mitochondrial cristae, as suggested previously. Conclusion: Using two super-resolution imaging approaches, this is the first study to show that in sections of human skeletal muscle PLIN2 and PLIN5 localize to the LD at distinct sites, with abundance of PLIN5 at LD-mitochondria tethering sites. This novel spatial information uncovers that PLIN proteins do not serve as lipolytic barriers but rather are docking sites for proteins facilitating selective lipase access under a variety of lipolytic conditions.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available