Piperazine-Based Mitochondria-Immobilized pH Fluorescent Probe for Imaging Endogenous ONOO- and Real-Time Tracking of Mitophagy.
ACS Appl Bio Mater
; 5(6): 2777-2785, 2022 06 20.
Article
em En
| MEDLINE
| ID: mdl-35574830
ABSTRACT
ONOO- is mainly produced in mitochondria, and dysfunctional and damaged mitochondria are degraded in lysosomes through autophagy, so it is important to synthesize a single probe for dual detection of ONOO- and mitophagy. Unfortunately, mitochondria-immobilized fluorescent probes for dual detection of ONOO- and mitophagy have not yet been developed. Hence, we first reported a piperazine-based mitochondria-immobilized red-emitting fluorescent probe (PMR), which not only can detect ONOO- but also could be used to image cellular mitophagy by the pH variations because of the protonation of the piperazine moiety. PMR was designed and prepared by introducing a piperazine ring as the pH response group, a lipophilic cation as the targeting mitochondria moiety, and benzyl chloride for immobilizing mitochondrial proteins through thiol groups. PMR displayed an enhanced fluorescence response at 640 nm through mitochondrial acidification. Using these advantages of PMR, which was successfully used for visualizing the mitophagy process induced by rapamycin or starvation, and chloroquine can inhibit rapamycin-induced mitophagy and prevent the fusion of autophagosomes and lysosomes. PMR also showed good sensitivity with a detection limit of 23 nM to ONOO-, which was successfully applied in imaging exogenous/endogenous ONOO-. Combining the above design, PMR may be used to study the detailed function of the mitophagy and ONOO--associated physiological and pathological processes.
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01-internacional
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MEDLINE
Assunto principal:
Mitofagia
/
Corantes Fluorescentes
Idioma:
En
Revista:
ACS Appl Bio Mater
Ano de publicação:
2022
Tipo de documento:
Article