Regulating Mitochondrial pH with Light and Implications for Chemoresistance

Abstract

Chemoresistance is one of the major challenges for cancer treatment, more recently ascribed to defective mitochondrial outer membrane permeabilization (MOMP), significantly diminishing chemotherapeutic agent‐induced apoptosis. A boron‐dipyrromethene (BODIPY) chromophore‐based triarylsulfonium photoacid generator (BD‐PAG) was used to target mitochondria with the aim to regulate mitochondrial pH and further depolarize the mitochondrial membrane. Cell viability assays demonstrated the relative biocompatibility of BD‐PAG in the dark while live cell imaging suggested high accumulation in mitochondria. Specific assays indicated that BD‐PAG is capable of regulating mitochondrial pH with significant effects on mitochondrial membrane depolarization. Therapeutic tests using chlorambucil in combination with BD‐PAG revealed a new strategy in chemoresistance suppression.

A BODIPY‐Based Far‐Red‐Absorbing Fluorescent Probe for Hypochlorous Acid Imaging

“…[3] The conventional method of HClO detection utilizes sodium thiosulfate and potassium iodide-starch indicators, cannot be applied to living cells, and cannot detect micromolar levels of HClO. [4] Fluorescent dyes have been widely used in chemosensors, [5] photodynamic therapy, [6] 3D data storage, [7] and biological imaging [8] due to their advantages in spatiotemporal control and selective response. Fluorescent probes with the real-time response of HClO have also been developed.…”

“…Fluorescent dyes have been widely used in chemosensors, [5] photodynamic therapy, [6] 3D data storage, [7] and biological imaging [8] due to their advantages in spatiotemporal control and selective response. Fluorescent probes with the real‐time response of HClO have also been developed [9–11] .…”

Novel Dual-Organelle-Targeting Probe (RCPP) for Simultaneous Measurement of Organellar Acidity and Alkalinity in Living Cells

“…Other organelles, including the lysosome, utilize this ATP to pump protons into the lumen to generate an acidic pH, which is required for the maturation and processing of secretory proteins . Mitochondria are alkaline, and mitochondrial acidification may result in mitochondrial autophagy and apoptosis. − Alterations of mitochondrial pH may induce cytochrome c release and opening of the mitochondrial permeability pore, and mitochondrial dysfunction as seen in cardiovascular and neurodegenerative disease. , Conversely, lysosomes have an acidic lumen (pH 4.0–6.0) and contain various proteases, which are active at acidic pH. Lysosomes contain hydrolases that facilitate the decomposition of proteins, lipids, and polysaccharides.…”

“…3−5 Alterations of mitochondrial pH may induce cytochrome c release and opening of the mitochondrial permeability pore, and mitochondrial dysfunction as seen in cardiovascular and neurodegenerative disease. 6,7 Conversely, lysosomes have an acidic lumen (pH 4.0−6.0) and contain various proteases, which are active at acidic pH. Lysosomes contain hydrolases that facilitate the decomposition of proteins, lipids, and polysaccharides.…”

Probing the flux of mitochondrial potassium using an azacrown-diketopyrrolopyrrole based highly sensitive probe

“…2,3 Consequently, many mitochondrial targeting potassium probes have been developed over the years. 4–7 Both the lipophilic triphenylphosphonium (TPP + ) moiety, 2 b , c ,5 quaternary ammonium salts 6,8 and triarylsulfonium salts 9 have been found to promote selective mitochondrial localization for fluorescent probes.…”