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

Mitochondria are central to the intrinsic apoptotic pathway of programmed cell death. Commitment to cell death occurs upon mitochondrial outer membrane permeabilization, and dysregulation of this vital apoptotic control point is implicated in various pathologies. Provided herein are novel sensors which can detect, in real time and with great sensitivity, the release of protons from intact mitochondria caused by mitochondrial outer membrane permeabilization. Embodiments include graphene based ion-sensitive field effect transistors.

The present disclosure highlights the relationship between extracellular mitochondrial components, optionally in combination with the secreted phospholipase A.sub.2-IIA and/or an auto-antibody, and in vivo as well as in vitro and inflammatory reactions/conditions, especially those released as a result of the degradation of a platelet. The present disclosure provides methods for determining the presence of inflammatory mediators, for limiting inflammatory reactions/conditions, for the diagnosis inflammatory reactions/conditions, for screening therapeutics for the treatment and/or the alleviation of symptoms of inflammatory reactions/conditions based on the detection or modulation of the level of these extracellular mitochondrial components.

Methods for staining mitochondria are disclosed involving using a composition containing a cationic species of the formula: (I) wherein at least one of Y and Z is a substituted or unsubstituted azetidine group; X is selected from O, S, SO.sub.2, Se, NR.sub.12, P(O)R.sub.12, CR.sub.13R.sub.14, SiR.sub.13R.sub.14, Te, and GeR.sub.13R.sub.14. Also disclosed are methods for analysing mitochondria, involving staining a sample of mitochondria. illuminating the stained sample using light of an appropriate wavelength to fluoresce the compound, and observing or imaging a magnified image of the sample.

##STR00001##

Embodiments herein include methods for enhancing post-ischemic functional recovery through administration of mitochondria and related devices and methods. In an embodiment, a method for enhancing post-ischemic functional recovery is included. The method can include harvesting somatic cells from a patient or a donor, converting the somatic cells into induced pluripotent stem cells, extracting mitochondria from the induced pluripotent stem cells, and transplanting the mitochondria into the patient. Other embodiments are also included herein.

The current invention pertains to a method of diagnosing a disease or identifying an increased likelihood of developing the disease in a subject. The method comprises determining the level of Src homology 3 domain binding protein 5 (SH3BP5 or SAB) or the RNA encoding SAB protein in a biological sample obtained from the subject and identifying the subject as having the disease or having an increased likelihood of developing the disease if the biological sample obtained from the subject has an altered level of SAB protein or the RNA encoding SAB protein relative to a control sample. The methods of the current invention can be practiced to diagnose and treat a systemic degenerative disease, a neurodegenerative disease, obesity, diabetes, a cancer, or an aging related disease. The invention also provides a kit for diagnosing a disease or diagnosing an increased likelihood of developing the disease in a subject.

Mitofusin modulatory peptides are described which may function as activators or inhibitors of mitochondrial fusion. The sequences and compositions comprising the sequences are useful for treating diseases or disorders associated with mitofusin 1 (Mfn1) and/or mitofusin 2 (Mfn2) and mitochondrial dysfunction. Methods of treatment, pharmaceutical formulations and methods of identifying compounds that mimic the activity of the peptides for use in screening assays are also described.

The invention provides methods, compositions, devices, and kits relating to the use of cholesterol-dependent cytolysins (e.g., PFOs) for measuring intracellular mitochondrial activity.

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.

An antibody has as a target molecule a ubiquitin protein comprising a phosphorylated serine residue at position 65. In addition, a method is provided for specifically detecting Parkinson's disease at an early stage, in which a target molecule is a ubiquitin protein comprising a phosphorylated serine residue at position 65, a pharmaceutical composition for definitively treating or preventing Parkinson's disease, and a method for screening for the pharmaceutical composition.