LysoTracker and MitoTracker Red are fluorescent probes widely used for viable cell staining of lysosomes and mitochondria, respectively. They are utilized to study organelle localization and their resident proteins, assess organelle functionality and quantification of organelle numbers. The ATP-driven efflux transporter P-glycoprotein (P-gp) is expressed in normal and malignant tissues and extrudes structurally distinct endogenous and exogenous cytotoxic compounds. Thus, once aromatic hydrophobic compounds such as the above-mentioned fluorescent probes are recognized as transport substrates, efflux pumps including P-gp may abolish their ability to reach their cellular target organelles. Herein, we show that LysoTracker and MitoTracker Red are expelled from P-gp-overexpressing cancer cells, thus hindering their ability to fluorescently mark target organelles. We further demonstrate that tariquidar, a potent P-gp transport inhibitor, restores LysoTracker and MitoTracker Red cell entry. We conclude that LysoTracker and MitoTracker Red are P-gp transport substrates, and therefore, P-gp expression must be taken into consideration prior to cellular applications using these probes. Importantly, as MitoTracker was a superior P-gp substrate than LysoTracker Red, we discuss the implications for the future design of chemotherapeutics evading cancer multidrug resistance. Furthermore, restoration of MitoTracker Red fluorescence in P-gp-overexpressing cells may facilitate the identification of potent P-gp transport inhibitors (i.e. chemosensitizers).
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http://dx.doi.org/10.1111/jcmm.13485 | DOI Listing |
J Ethnopharmacol
December 2024
Heilongjiang University of Chinese Medicine, Key Laboratory of Basic and Application Research of Beiyao (Heilongjiang University of Chinese Medicine), Ministry of Education Heilongjiang Touyan Innovation Team Program, Harbin 150040, P.R.China. Electronic address:
Ethnopharmacological Relevance: In the realm of traditional Chinese medicine, Panax quinquefolius L. has garnered significant attention for its potential to treat various ailments associated with deficiencies, including qi, blood, and kidneys. As its primary bioactive constituent, Panax quinquefolius saponins (PQS) have the potential therapeutic role of Alzheimer's disease (AD) treatment, but with unclear mechanisms of action.
View Article and Find Full Text PDFMethods Mol Biol
November 2024
MIA - Multidisciplinary Institute of Ageing, University of Coimbra, Coimbra, Portugal.
Live cell imaging is a robust method to visualize dynamic cellular structures, especially organelles with network-like structures such as mitochondria. In this regard, mitochondrial dynamics, namely mitochondrial fission and fusion, are highly dynamic processes that regulate mitochondrial size and morphology depending on a plethora of cellular cues. Likewise, lysosome size and distribution may hint at their function and state.
View Article and Find Full Text PDFRedox Biol
September 2024
Department of Hepatobiliary Surgery, Hunan Provincial People's Hospital (The First Affiliated Hospital of Hunan Normal University), Changsha, 410005, China; Hunan Engineering Research Center of Digital Hepatobiliary Medicine, Changsha, 410005, China; Hunan Key Laboratory for the Prevention and Treatment of Biliary Tract Diseases, Changsha, 410005, China. Electronic address:
Background: Mitochondrial dysfunction and metabolic reprogramming can lead to the development and progression of hepatocellular carcinoma (HCC). Ferredoxin 1 (FDX1) is a small mitochondrial protein and recent studies have shown that FDX1 plays an important role in tumor cuproptosis, but its role in HCC is still elusive. In this study, we aim to investigate the expression and novel functions of FDX1 in HCC.
View Article and Find Full Text PDFAnn Clin Lab Sci
March 2024
Department of Pathology, Brooklyn, NY, USA
Objective: We have previously shown that the anti-cancer peptide PNC-27 kills cancer cells by co-localizing with membrane-expressed HDM-2, resulting in transmembrane pore formation causing extrusion of intracellular contents. We have also observed cancer cell mitochondrial disruption in PNC-27-treated cancer cells. Our objectives are to determine: 1.
View Article and Find Full Text PDFEpilepsia Open
August 2024
Department of Neurology, The Affiliated Hospital of Zunyi Medical University, Zunyi, China.
Objective: The objective of this study is to determine whether inhibition of mitophagy affects seizures through Clathrin-mediated endocytosis (CME).
Methods: Pentylenetetrazol (PTZ) was intraperitoneally injected daily to establish a chronic PTZ-kindled seizure. The Western blot (WB) was used to compare the differences in Parkin protein expression between the epilepsy group and the control group.
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