Light-Up Mitophagy in Live Cells with Dual-Functional Theranostic Phosphorescent Iridium(III) Complexes

Phosphorescent
Ir­(III) complexes are expected to be new multifunctional theranostic
platforms that enable the integration of imaging capabilities and
anticancer properties. Mitophagy is an important selective autophagic
process that degrades dysfunctional mitochondria. Until now, the regulation
of mitophagy is still poorly understood. Herein, we present two phosphorescent
cyclometalated iridium­(III) complexes (Ir1 and Ir2) that can accumulate in mitochondria and induce mitophagy.
Because of their intrinsic phosphorescence, they can specially image
mitochondria and track mitochondrial morphological alterations. Mechanism
studies show that Ir1 and Ir2 induce mitophagy
by depolarization of mitochondrial membrane potential, depletion of
cellular ATP, perturbation in mitochondrial metabolic status, and
induction of oxidative stress. Moreover, no sign of apoptosis is observed
in Ir1- and Ir2-treated cells under the
same conditions that an obvious mitophagic response is initiated.
We demonstrate that Ir1 is a promising theranostic agent
that can induce mitophagy and visualize changes in mitochondrial morphology
simultaneously.