The present disclosure relates to methods of identifying patients that may be responsive to mitochondrial inhibitor therapies to target and eradicate cancer stem cells. Also described are diagnostic kits that may be used to identify patients responsive to mitochondrial inhibitor therapies.

Mitochondria-targeting potassium sensors and method(s) for making such sensors. The sensor shows a response to potassium and displays a 130-fold dynamic range of fluorescence intensity and high brightness. The sensors response to potassium concentrations was demonstrated to be unaffected by cellular pH value and/or concentrations of other ions. The sensors can be used for monitoring the mitochondrial potassium efflux/influx.

A system, and method, for quantitatively mapping of mitochondrial membrane potential of a tissue in a subject is provided. In some aspects, the provided method includes administering to the subject a detectably effective amount of a tracer as an emission tomography imaging agent; acquiring, using an emission tomography system, emission tomography data associated with the tissue; analyzing the emission tomography data to determine a concentration distribution of the tracer within the tissue; correlating the concentration distribution of the tracer with the membrane potential of the tissue; determining, using the correlating step, a membrane potential distribution of the tissue; and generating a report indicating the membrane potential distribution of the tissue.

The disclosure provides compositions and methods relating to aromatic-cationic peptides. The methods comprise administering to the subject an effective amount of an aromatic-cationic peptide to subjects in need thereof For example, the peptides may be administered to subjects in need of a mitochondrial-targeted antioxidant.

The present invention relates to a method and/or assay for the assessment of the metabolic effect of a candidate compound. The method and/or assay comprises exposing one or more 3-dimensional cell culture or tissue to one or more candidate compounds, and measuring, in at least one 3-dimensional cell culture or tissue, the effect of such exposure on the 3-dimensional cell culture or tissue-specific respiration rate (MTSRR) (FIG. 1B).

Disclosed is a pH-responsive fluorescent compound, represented by the general formula, which is a novel pH-responsive fluorescent compound capable of being specifically localized in mitochondria within cells, which exhibits strong fluorescence under weakly acidic pH environments in lysosomes, and which is not readily subject to interference from autofluorescence and background fluorescence due to other fluorescent substances within cells. Also disclosed are a composition for detecting mitophagy using the pH-responsive fluorescent compound, and a method for detecting mitophagy within cells.

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In the general formula, L represents a linker, X represents a pharmaceutically acceptable anion, and Y represents a reactive group that may react with a functional group on a mitochondrial protein to form a covalent bond.

The present disclosure provides diagnostic methods useful for predicting a patient's response to alvocidib and guiding a physician decision to administer alvocidib to the patient.

Methods of promoting hypoxia or the hypoxia response for the treatment or prevention of mitochondrial dysfunction and oxidative stress disorders are described. Methods for screening for targets of mitochondrial dysfunction and oxidative stress disorders are also described.

A method of manipulating and/or investigating cellular bodies (9) is provided. The method comprises the steps of: providing a sample holder (3) comprising a holding space (5) for holding a fluid medium (11); providing a sample (7) comprising one or more cellular bodies (9) in a fluid medium (11) in the holding space (5); generating an acoustic wave in the holding space exerting a force (F) on the sample (7) in the holding space (5). The method further comprises providing the holding space (5) with a functionalised wall surface portion (17) to be contacted by the sample (7) and the sample (7) is in contact with the functionalised wall surface portion (17) during at least part of the step of application of the acoustic wave. A system and a sample holder (3) are also provided.

The present disclosure is generally directed to profiling peptides, compositions, and kits, as well as methods of use thereof. The profiling peptides comprise an Mcl-1 binding domain, and optionally a cellular uptake moiety. The methods of using such profiling peptides include predicting sensitivity of a cancer, selecting a treatment, treating a cancer, producing a sensitivity profile, and the like.