Artificially inducing close apposition of endoplasmic reticulum and mitochondria induces mitochondrial fragmentation.

Abstract

Cycles of mitochondrial fission and fission are essential for normal cell physiology. Defects in the machinery controlling these processes lead to neurodegenerative disease. While we are beginning to understand the machinery that drives fission, our knowledge of the spatial and temporal control of this event is lacking. Here we use a rapamycin-inducible heterodimerization system comprising both ER and mitochondrial transmembrane components to bring the ER membrane into close physical proximity with mitochondria. We show that this artificial apposition of membranes is sufficient to cause rapid mitochondrial fragmentation. Resulting mitochondrial fragments are shown to be distinct entities using fluorescence recovery after photobleaching. We also show that these fragments retain a mitochondrial membrane potential. In contrast, inducible tethering of the peripheral ER exit site protein TFG does not cause mitochondrial fragmentation suggesting that very close apposition of the two membranes is required.