Rapid manipulation of mitochondrial morphology in a living cell with iCMM

Abstract

Summary: Engineered synthetic biomolecular devices that integrate elaborate information processing and precisely regulate living cell behavior have potential in various applications. Although devices that directly regulate key biomolecules constituting inherent biological systems exist, no devices have been developed to control intracellular membrane architecture, contributing to the spatiotemporal functions of these biomolecules. This study developed a synthetic biomolecular device, termed inducible counter mitochondrial morphology (iCMM), to manipulate mitochondrial morphology, an emerging informative property for understanding physiopathological cellular behaviors, on a minute timescale by using a chemically inducible dimerization system. Using iCMM, we determined cellular changes by altering mitochondrial morphology in an unprecedented manner. This approach serves as a platform for developing more sophisticated synthetic biomolecular devices to regulate biological systems by extending manipulation targets from conventional biomolecules to mitochondria. Furthermore, iCMM might serve as a tool for uncovering the biological significance of mitochondrial morphology in various physiopathological cellular processes. Motivation: Mitochondria exhibit a variety of morphologies depending on the physiopathological condition of the cell, but the significance of changes in mitochondrial morphology remains almost unresolved. Although a method to induce mitochondrial morphological changes by altering the expression of proteins involved in mitochondrial dynamics has been established, this method requires several hours or more to induce mitochondrial morphological changes. Accordingly, a method to induce mitochondrial morphological changes at any given point in time on a minute timescale is needed.

Keywords

• mitochondria
• mitochondrial morphology
• synthetic biocomputing device
• synthetic biology
• Boolean logic gate