期刊
NATURE COMMUNICATIONS
卷 13, 期 1, 页码 -出版社
NATURE PORTFOLIO
DOI: 10.1038/s41467-022-31946-5
关键词
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资金
- National Institutes of Health [R01GM136858, 1DP2 NS111133-01]
- Chang-Zuckerberg Initiative
- Strategic Research Support Fund of Kagawa University Research Promotion Program 2021 (KURPP)
- Charitable Trust MIU Foundation Memorial Fund
- World Premier International Research Center Initiative (WPI), MEXT, Japan
- Takeda Science Foundation
- Uehara Memorial Foundation
In this study, the authors developed a tool using phospholipase A/acyltransferases (PLAATs) to rapidly defunctionalize organelles by remodeling the membrane phospholipids. They showed that this method is versatile and compatible with various experimental techniques and can be applied to study organelle biology.
Approaches for manipulating individual organelles are important for learning more about their functions. Here the authors report a tool utilising phospholipase A/acyltransferases (PLAATs) for rapid defunctionalisation of organelles through remodelling of the membrane phospholipids. Organelles vitally achieve multifaceted functions to maintain cellular homeostasis. Genetic and pharmacological approaches to manipulate individual organelles are powerful in probing their physiological roles. However, many of them are either slow in action, limited to certain organelles, or rely on toxic agents. Here, we design a generalizable molecular tool utilizing phospholipase A/acyltransferases (PLAATs) for rapid defunctionalization of organelles via remodeling of the membrane phospholipids. In particular, we identify catalytically active PLAAT truncates with minimal unfavorable characteristics. Chemically-induced translocation of the optimized PLAAT to the mitochondria surface results in their rapid deformation in a phospholipase activity dependent manner, followed by loss of luminal proteins as well as dissipated membrane potential, thus invalidating the functionality. To demonstrate wide applicability, we then adapt the molecular tool in peroxisomes, and observe leakage of matrix-resident functional proteins. The technique is compatible with optogenetic control, viral delivery and operation in primary neuronal cultures. Due to such versatility, the PLAAT strategy should prove useful in studying organelle biology of diverse contexts.
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