The present invention provides a drug for a pathological condition including mitochondria-related disease by a conjugate of a double-membrane organelle DNA sequence recognizing compound and a double-membrane organelle localizable compound. The present invention provides a conjugate in which a double-membrane organelle localizable lipophilic cation is attached to linear PI polyamide that specifically binds to a double-membrane organelle DNA sequence, a linear PI polyamide-TPP conjugate targeting the mitochondrial DNA mutation or polymorphism, comprising the conjugate, and a pharmaceutical composition comprising the conjugate.

Mitochondrial respirometry is used to study mitochondrial functionality in healthy tissues as well as mitochondrial diseases or diseases having a link to mitochondrial function such as diabetes mellitus type 2, obesity and cancer. However, barriers to studying energy metabolism are high due to the limitations of conventional technologies which require the analysis of living or freshly isolated biological specimens. The invention disclosed herein provides a new technology to assess cellular energy production capacity in previously frozen biological specimens.

Aspects of the application provide methods and compositions for identifying and evaluating putative therapeutic agents for cancer by live cell imaging. Cell samples comprising cancerous cells that have been pre-treated with a test agent are contacted with a BH3 peptide, and samples are imaged by live cell imaging over a time interval. Methods of the application can be used to determine whether a patient is likely to benefit from treatment with a particular test agent.

There is provided a method of targeting mitochondrial biogenesis and mitochondrial transport from the cell body to axon to protect acutely demyelinated axons from degeneration. The method may comprise increasing mobilization of mitochondria from the neuronal cell body to the demyelinated axon to treat demyelinating disorders and provide a novel neuroprotective strategy for vulnerable acutely demyelinated axons. The method may comprise mitochondrial biogenesis in the demyelinated axon to treat demyelinating disorders and provide a novel neuroprotective strategy for vulnerable acutely demyelinated axons. The method comprises a variety of compounds and strategies for increasing mitochondrial transport and biogenesis to the demyelinated axon in both the peripheral and central nervous systems.

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 invention relates to a novel near-infrared fluorescent probe having specificity for mitochondria due to a hydrophobic group attached to a silicon-rhodamine core, and the use thereof for mitochondrial detection and cancer diagnosis. The fluorescent probe of the present invention has improved mitochondrial targeting efficiency compared to conventional probes due to a hydrophobic group attached to a silicon-rhodamine core, can detect mitochondria in living tissue with high sensitivity and specificity in a near-infrared (NIR) region (700 to 1,700 nm), and can acquire three-dimensional high-resolution biological images without harming the human body. Due to these advantages, the fluorescent probe can be used not only for mitochondrial detection in cells in the laboratory, but also as a contrast agent or a drug delivery carrier in cancer diagnosis and surgery.

The present invention encompasses the use of compounds for a novel approach to treat and prevent diseases, conditions, and disorders such as diabetes and ischemic reperfusion injury. Compounds of the invention, including but not limited to BAM15 ((2-fluorophenyl){6-[(2-fluorophenyl)amino](1,2,5-oxadiazolo[3,4-e]pyrazin-5-yl)}amine), a mitochondrial uncoupler, can improve glucose tolerance, increases cellular oxygen consumption, treat or prevent kidney ischemia reperfusion injury reverse insulin resistance, reverse or treat hyperinsulinemia, and reverse or treat hyperlipidemia. The present invention further provides novel compounds as well as methods for identifying compounds with the same or similar properties as BAM15.

The present invention provides methods of predicting cell sensitivity or resistance to a therapeutic agent.

Disclosed herein are methods for improving exosome production or stimulating exosome secretion by cells. The methods comprise inhibiting at least one step of the glycolytic pathway by contacting the cells with at least one glycolytic inhibitor and/or inhibiting mitochondrial function by contacting the cells with at least one inhibitor of mitochondrial function.

Disclosed herein is a recombinant human cell line that does not express functional endogenous NADH dehydrogenase [ubiquinone] iron-sulfur protein 2 (NDUFS2). This knockout cell line can be used to advance the basic understanding of the NDUFS2 protein subunit in overall complex I assembly and function. Furthermore, this cell line can be used to test therapeutic agents to fix or bypass the dysfunctional complex I.