The present disclosure concerns methods of detecting injury to a tissue and/or organ in a subject. In some aspects, the subject is the recipient of a transplant, such as a liver transplant. In some aspects, the subject is undergoing treatment with an immunosuppressant. In some aspects, the present disclosure concerns the identification of aberrant mitochondria in the subject to identify injury to the tissue and/or organ of the subject. Detecting aberrant mitochondria allows for remedial and/or corrective action to prevent or avoid significant injury.

This disclosure provides a screening method to identify Parkin-mediated mitophagy activating agents wherein the method comprises contacting cells exogenously expressing labelled mutant Parkin polypeptide with a test agent and a mitophagy inducing agent, and measuring the amount of Parkin polypeptide recruited to mitochondria in the cells. Also provided is a kit comprising a plasmid, recombinant cells, a multi-well plate, a pintool head, cells expressing wildtype Parkin, and transfection reagents.

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.

Compositions and methods for treatment of mitochondrial respiratory chain dysfunction and other mitochondrial disorders are provided. Also disclosed are a number of screening assays having utility for the identification of agents which modulate the phenotype associated with mitochondrial respiratory chain dysfunction.

The present invention provides methods of assessing toxicity using Dynamic BH3 profiling.

An automated isolation device for isolation of mitochondria includes an incubation station including a holder for a viable mitochondria solution; and a cooling system, controlled by a processor of the device, for cooling the holder. The device includes a processor-controlled transfer system for transferring solution from the holder to a filtration station; and the filtration station, including a series of filters. The device includes a processor-controlled spectrometry station including a spectrometer positioned to illuminate a cuvette fluidically coupled to an output of the filtration station; and a detector coupled to the processor and positioned on a side of the cuvette opposite the spectrometer. The device includes a processor-controlled transfer system for transferring solution from the spectrometry station to a centrifuge. The centrifuge is processor-controlled and configured to centrifuge the filtrate to separate viable mitochondria from a supernatant.

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.

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.

Mitochondrial function is measured. Repetitive or continuous measurements are performed of prompt red fluorescence, emerging from the skin due to PpIX build up, and/or delayed fluorescence of PpIX. An estimate of the rate of PpIX generation is used as an indicator of mitochondrial integrity and ATP availability. Mitochondrial oxygen tension is determined from the delayed fluorescence lifetime of PpIX. When blood supply to the measurement volume is interrupted or reduced, the resulting changes to the mitochondrial oxygen tension allow an estimation of information about the kinetics of oxygen consumption in the mitochondria, such as the maximum rate of oxygen consumption as well as the Michaelis-Menten constant, providing information about the oxygen affinity of the mitochondrial respiratory chain.

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.