Details

Autor(en) / Beteiligte

• Kathayat, Rahul S
• Cao, Yang
• Elvira, Pablo D
• Sandoz, Patrick A
• Zaballa, María-Eugenia
• Springer, Maya Z
• Drake, Lauren E
• Macleod, Kay F
• van der Goot, F Gisou
• Dickinson, Bryan C

Titel

Active and dynamic mitochondrial S-depalmitoylation revealed by targeted fluorescent probes

Ist Teil von

• Nature communications, 2018-01, Vol.9 (1), p.334-14, Article 334

Ort / Verlag

England: Nature Publishing Group

Erscheinungsjahr

2018

Quelle

MEDLINE

Beschreibungen/Notizen

• The reversible modification of cysteine residues by thioester formation with palmitate (S-palmitoylation) is an abundant lipid post-translational modification (PTM) in mammalian systems. S-palmitoylation has been observed on mitochondrial proteins, providing an intriguing potential connection between metabolic lipids and mitochondrial regulation. However, it is unknown whether and/or how mitochondrial S-palmitoylation is regulated. Here we report the development of mitoDPPs, targeted fluorescent probes that measure the activity levels of "erasers" of S-palmitoylation, acyl-protein thioesterases (APTs), within mitochondria of live cells. Using mitoDPPs, we discover active S-depalmitoylation in mitochondria, in part mediated by APT1, an S-depalmitoylase previously thought to reside in the cytosol and on the Golgi apparatus. We also find that perturbation of long-chain acyl-CoA cytoplasm and mitochondrial regulatory proteins, respectively, results in selective responses from cytosolic and mitochondrial S-depalmitoylases. Altogether, this work reveals that mitochondrial S-palmitoylation is actively regulated by "eraser" enzymes that respond to alterations in mitochondrial lipid homeostasis.