Mitokyne: A Ratiometric Raman Probe for Mitochondrial pH

Abstract

Mitochondrial pH (pHmito) is intimately related to mitochondrial function, and aberrant values for pHmito are linked to several disease states. We report the design, synthesis, and application of mitokyne 1the first small molecule pHmito sensor for stimulated Raman scattering (SRS) microscopy. This ratiometric probe can determine subtle changes in pHmito in response to external stimuli and the inhibition of both the electron transport chain and ATP synthase with small molecule inhibitors. In addition, 1 was also used to monitor mitochondrial dynamics in a time-resolved manner with subcellular spatial resolution during mitophagy providing a powerful tool for dissecting the molecular and cell biology of this critical organelle.

Ni(II) Ions May Target the Entire Melatonin Biosynthesis Pathway—A Plausible Mechanism of Nickel Toxicity

“…Based on the above analysis, our results imply that the enzymes from the melatonin biosynthesis pathway, acetylserotonin O -methyltransferase in particular, are the toxicological targets for Ni(II) ions. It seems especially possible because melatonin is synthesized in mitochondria, which are known to contain pH more basic than the cytoplasm [ 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 ].…”

“…The cleavage is pH-dependent, and Ni(II) ions break proteins relatively slowly at pH 7.4, but much more rapidly in locations with higher pH [ 7 ]. Interestingly, pH values in the mitochondrial matrix are high enough [ 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 ] to facilitate Ni(II)-assisted hydrolysis of the peptide bond.…”

Multichannel Fluorescence Microscopy: Advantages of Going beyond a Single Emission

“…[ 149 ] As an example, specific ratiometric sensors for SRS can be developed for the detection of intracellular pH. [ 156 ]…”

“…[149] As an example, specific ratiometric sensors for SRS can be developed for the detection of intracellular pH. [156] Raman markers can also be designed to present distinctive Raman spectra that can be easily distinguished, in comparison to the bulk Raman spectra of a sample that is composed by the superposition of the different spectrum of each molecule. This allows multiplexing because each of the markers can target a specific biomolecule that can be detected using the specific Raman spectrum of the marker.…”

Upconversion fluorescent nanoprobe based on the 4-NP reversible structure for a wide range of pH determination

“…pH is an important parameter in many fields. The determination of wastewater pH, [1][2][3] soil pH, 4 medicine pH [5][6][7] and food pH 8 is of great significance in the fields of industry, agriculture, medicine and food safety testing. Any chemical reaction or biological process needs to initiate a delicate balance of parameters, and hydrogen ion concentration (pH) is an important parameter that needs to be precisely controlled.…”