Small-Molecule Fluorogenic Probe for the Detection of Mitochondrial Temperature In Vivo

Abstract

Mitochondria, as energy factories, participate in many metabolic processes and play vital roles in cell life. Most human diseases are caused by mitochondrial dysfunction, and mitochondrial temperature is an important indicator of mitochondrial function. Despite the biological importance of mitochondria, there are few tools for detecting changes in mitochondrial temperature in living organisms. Here, we report on a thermosensitive rhodamine B (RhB)-derived fluorogenic probe (RhBIV) that enables fluorescent labeling of cell mitochondria at concentrations as low as 1 μM. We demonstrate that this probe exhibits a temperature-dependent response in cell mitochondria. Furthermore, in mice, it has a long half-life (t 1/2 ) and is primarily enriched in the liver. This unique thermosensitive probe offers a simple, nondestructive method for longitudinal monitoring of mitochondrial temperature both in vitro and in vivo to elucidate fundamental physiological and pathological processes related to mitochondrial function.

Recent progress on small molecular temperature‐sensitive fluorescent probes

“…Bai group reported a thermosensitive RhB‐derived fluorogenic probe (RhBIV) that enabled fluorescent labeling of cell mitochondria at concentrations as low as 1 μM (Figure 6a) (F. Shen et al, 2021). In comparison of the commercially available RhB, the excitation and emission wavelengths of RhBIV red‐shift to 520 and 592 nm, respectively.…”

Visible light responsive photoacids for subcellular pH and temperature correlated fluorescence sensing

“…1 For example, subcellular temperature sensing may help provide information about gene expression, cell division, and enzyme reaction. [2][3][4] Previously, cellular temperature sensors have been designed based on different materials, including synthetic dyes, [5][6][7] fluorescent proteins, 8,9 dye-doped thermo-sensitive polymers, 2,10,11 quantum dots, [12][13][14] carbon dots, 15,16 vacancy-containing nanodiamonds, 17,18 and so on. 19 Synthetic photoswitchable compounds have opened new avenues in various chemical and biological fields 20 such as photopharmacology, [21][22][23] fluorescence microscopy, [24][25][26] and chemical sensing.…”

“…1 For example, subcellular temperature sensing may help provide information about gene expression, cell division, and enzyme reaction. 2–4 Previously, cellular temperature sensors have been designed based on different materials, including synthetic dyes, 5–7 fluorescent proteins, 8,9 dye-doped thermo-sensitive polymers, 2,10,11 quantum dots, 12–14 carbon dots, 15,16 vacancy-containing nanodiamonds, 17,18 and so on. 19…”

Ultrasensitive Small-Molecule Fluorescent Thermometer Reveals Hot Mitochondria in Surgically Resected Human Tumors

“…In addition, the RhBIV probe, a small-molecule fluorescent mitochondria-targeted thermometer was successfully developed by the introduction of a piperidine group to rhodamine B. 22 The probe fluorescence decreased by 3.92% for every 1 °C elevation, which could monitor the mitochondrial temperature both in vitro and in vivo. It is noted that most of these reported small-molecule probes are constructed by utilizing rhodamine as the temperature-sensitive group.…”

“…The probe determined that the variation of mitochondrial temperature is closely related to inflammation. In addition, the RhBIV probe, a small-molecule fluorescent mitochondria-targeted thermometer was successfully developed by the introduction of a piperidine group to rhodamine B . The probe fluorescence decreased by 3.92% for every 1 °C elevation, which could monitor the mitochondrial temperature both in vitro and in vivo .…”