Mild Depolarization of Mitochondria as a Mechanism of an Anti-Aging Program Which Is Opposed to Aging Program

Vyssokikh, M.Y.; Holtze, Susanne; Averina, Olga A.; Lyamzaev, Konstantin G.; Panteleeva, Alisa A.; Marey, Maria V.; Zinovkin, Roman A.; Severin, Fedor F.; Скулачев, М. В.; Hildebrandt, Thomas B.; Skulachev, Vladimir P.; Perinatology,

doi:10.30826/homosapiens-2020-23

Proceedings of the 3rd International Conference in Celebration of the 85th Birthday of Professor V.P. Skulachev. Abstract Book 2020

DOI: 10.30826/homosapiens-2020-23

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Mild Depolarization of Mitochondria as a Mechanism of an Anti-Aging Program Which Is Opposed to Aging Program

M.Y. Vyssokikh¹,

Susanne Holtze²,

Olga A. Averina³

et al.

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“…However, in contrast to other intracellular organelles, mitochondria are challenging to target due to their unique double layer membrane as well as extremely negative potential of inner mitochondrial membrane (IMM) [(ΔΨ m ) cancer ≈ −220 mV] which act as a fence for the uptake of molecules. 38 We exploited the unusual biophysical membrane property of malignant mitochondria to target IMM. Herein, the FF dipeptide anchored with unsymmetrical visible Cy−3 and NIR Cy−5 chromophores comprising a mitochondria specific triphenylphosphonium (TPP + ) group are constructed using a microwave (MW)-aided Fmoc solid phase peptide synthesis (SPPS) procedure on the Wang resin.…”

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Supramolecular Dipeptide-Based Near-Infrared Fluorescent Nanotubes for Cellular Mitochondria Targeted Imaging and Early Apoptosis

et al. 2021

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Herein, we have designed and synthesized unsymmetrical visible Cy–3 and near-infrared (NIR) Cy–5 chromophores anchoring mitochondria targeting functional group conjugated with a Phe-Phe dipeptide by a microwave-assisted Fmoc solid phase peptide synthesis method on Wang resin. These dipeptide-based Cy–3-TPP/FF as well as Cy–5-TPP/FF molecules self-assemble to form fluorescent nanotubes in solution, and it has been confirmed by TEM, SEM, and AFM. The Cy–3-TPP/FF and Cy–5-TPP/FF molecules in solution exhibit narrow excitation as well as emission bands in the visible and NIR region, respectively. These lipophilic cationic fluorescent peptide molecules spontaneously and selectively accumulate inside the mitochondria of human carcinoma cells that have been experimentally validated by live cell confocal laser scanning microscopy and display a high Pearson’s correlation coefficient in a colocalization assay. Live cell multicolor confocal imaging using the NIR Cy–5-TPP/FF in combination with other organelle specific dye is also accomplished. Moreover, these lipophilic dipeptide-based cationic molecules reach the critical aggregation concentration inside the mitochondria because of the extremely negative inner mitochondrial membrane potential [(ΔΨm)cancer ≈ −220 mV] and form supramolecular nanotubes which are accountable for malignant mitochondria targeted early apoptosis. The early apoptosis is arrested using Cy–5-TPP/FF and confirmed by annexin V-FITC/PI apoptosis detection assay.

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Supramolecular Dipeptide-Based Near-Infrared Fluorescent Nanotubes for Cellular Mitochondria Targeted Imaging and Early Apoptosis

et al. 2021

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Mild Depolarization of Mitochondria as a Mechanism of an Anti-Aging Program Which Is Opposed to Aging Program

Cited by 1 publication

References 0 publications

Supramolecular Dipeptide-Based Near-Infrared Fluorescent Nanotubes for Cellular Mitochondria Targeted Imaging and Early Apoptosis

Supramolecular Dipeptide-Based Near-Infrared Fluorescent Nanotubes for Cellular Mitochondria Targeted Imaging and Early Apoptosis

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