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 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.

The invention is directed to a method for identifying a candidate anti-glioma drug that is a mitochondrial F.sub.1F.sub.o ATP Synthase c-subunit leak channel opener, the method comprising: a. providing an admixture comprising: i. a candidate drug; ii. a submitochondrial vesicle (SMV) preparation; and iii. an H.sup.+ probe, wherein the H.sup.+ probe remains outside of the SMV(s); b. contacting the admixture with ATP; c. measuring a level of H.sup.+ outside of the SMV(s) via the H.sup.+ probe; d. comparing the level of H.sup.+ at step c) with a level of H.sup.+ in a control admixture lacking the candidate drug; and identifying the drug as a candidate anti-glioma drug that is a mitochondrial F.sub.1F.sub.o ATP Synthase c-subunit leak channel opener, when the level of H.sup.+ is higher compared to the level of H.sup.+ in the control admixture; or identifying that the drug is not a candidate anti-glioma drug that is a mitochondrial F.sub.1F.sub.o ATP Synthase c-subunit leak channel opener, when the level of H.sup.+ is the same or lower compared to the level of H.sup.+ in the control admixture.

The present application relates to methods of treating a subject with a disease or disorder associated with a mitochondrial deficit, comprising: determining at least one of a type or degree of the mitochondrial deficit in the subject; and administering an amount of a butyrate compound to the subject based at least partially on the determining step so as to promote Adenosine triphosphate (ATP) production in the subject as well as to methods of screening for compounds that restore cellular mitochondrial activity.

The present invention relates to compositions and methods for cancer treatment comprising compounds of Formulae I, II, and III. In some aspects, the invention relates to the treatment of B-cell Lymphoma or other hematopoietic cancers. In other aspects, the invention provides methods for treating particular types of hematopoietic cancers, such as, for example, B-cell lymphoma, using a combination of one or more compounds of Formulae I, II, and III. Combination therapy with, for example, 26S proteasome inhibitors, such as, for example, Bortezomib, are also included. In another aspect the present invention relates to autoimmune treatment with compounds of Formulae I, II, and III. In another aspect, this invention relates to methods for identifying compounds, for example, compounds of the BH3 mimic class, that have in vitro properties that predict in vivo efficacy against B-cell lymphoma tumors and other cancers as well as autoimmune disease.

The present invention provides compounds that modulate protein translocation in mitochondria, compositions thereof, and methods of identifying, making and using these.

The invention relates generally to systems and methods of bioenergetic profiling, uses thereof, and systems and devices relating thereto. In particular, methods of the invention are useful in assessing wellness, particularly in elderly subjects. Described are systems and methods of assessing likelihood of subject morbidity, life expectancy, positive clinical outcome, responsiveness to treatment, and certain disease states as well as of selecting treatment strategy, improving outcome to treatment strategy, and treating subjects with low bioenergetic profiles. Also described are devices and systems for measuring respiratory capacity.

The present disclosure provides a method of identifying factors for the treatment of mitochondrial and age-related diseases and disorders. Identification of the factors can comprise, e.g., biochemical, genomic, transcriptomic, proteomic and metabolomic analyses. The factors include proteins (e.g., cytokines) whose production or secretion into the blood is stimulated by exercise. The factors can be developed into therapeutics for the treatment of mitochondrial and age-related diseases and disorders.

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.

The present invention relates provides methods of predicting cell sensitivity to a test agent. In some embodiments, the cells are cultured in a culture medium having serum.