Mitochondrial Research | SAPRA Biomedicals

Elucidate the interplay between mitochondrial electron transport and mitophagy, and develop therapeutics to treat mitochondrial dysfunction

Mitochondria are the cellular organelles responsible for converting the food and oxygen into energy. Thus, these maternally inherited tiny organelles are considered as the power houses of the cell. Disorders in mitochondrial function lead to disease in organs or tissues that have greater energy demands, such as, brain, eye, heart, muscles, liver, and endocrine systems. Mitochondrial dysfunction underlies many of the most common chronic diseases, including cardiovascular disease, diabetes, neurological disorders, cancer, and aging. Mitochondrial diseases affect one in 5,000 people throughout the world.

We perform the following in our efforts to rescue mitochondrial dysfunction:

1. Construct CRISPR knockout cell models mimicking mitochondrial electron transport dysfunctions of human embryonic kidney (HEK293) cells

We will provide CRISPR knockout mutants of human and mouse cell lines

2. Construct CRISPR knockout cardiomyocytes and neurons mimicking mitochondrial electron transport dysfunctions of induced pluripotent stem cells (iPSC)

3. Screen compound libraries to identify novel drug candidates to restore mitochondrial electron transport and mitochondrial integrity (mitophagy)

Our Relevant Publications

Bandara, A.B., Drake, J.C., James, C.C., Smyth, J.W., Brown D.A.: Complex I protein NDUFS2 is vital for growth, ROS generation, membrane integrity, apoptosis, and mitochondrial energetics. Mitochondrion 2021, 58:160-168. PMID: 33744462. PMCID: PMC8113094. DOI: 10.1016/j.mito.2021.03.003.

Bandara, A.B., J.C. Drake, and D.A. Brown. Complex II subunit SDHD is critical for cell growth and metabolism, which can be partially restored with a synthetic ubiquinone analog. BMC Mol Cell Biol 2021, 22(1):35. PMID: 34118887. PMCID: PMC8196461. DOI: 10.1186/s12860-021-00370-w.

Drake, J.C., Wilson, R.J., Bandara, A.B. et al. Mitochondria-localized AMPK responds to local energetics and contributes to exercise and energetic stress-induced mitophagy. Proc Natl Acad Sci USA. 2021. 118(37):e2025932118. doi:10.1073/pnas.2025932118. PMID: 34493662. PMCID: PMC8449344. DOI: 10.1073/pnas.2025932118.

Brisendine M.H., A.S. Nichenko, A.B. Bandara, O.S. Willoughby, J.C. Drake. 2023. Neuromuscular Dysfunction Precedes Cognitive Impairment in a Mouse Model of Alzheimer's Disease. Function (Oxf). 2023 Dec 4;5(1):zqad066. PMID: 38111538. PMCID: PMC10727840. DOI: 10.1093/function/zqad066.