Research and Funding

Rare diseases present unique opportunities to unravel complex or elusive mechanisms and pathways in human health and common disorders. Through collaborative efforts, we identified and characterized two rare mitochondrial diseases caused by pathogenic mutations in the LONP1 gene. LonP1 is an indispensable mitochondrial ATP-dependent protease, molecular chaperone and DNA-binding protein, which plays multifaceted roles in maintaining cellular homeostasis and responding to cell stress.

Current work in the Suzuki lab leverages primary and patient-derived stem cells using innovative approaches to elucidate integrated mechanisms governing mitochondrial DNA and RNA dynamics. These mechanisms are regulated by LonP1 and TFAM, an essential mitochondrial transcription factor that also acts as a histone-like protein. Additionally, we delve into how oxidative metabolism is fine-tuned by the interplay of LonP1 and the pyruvate dehydrogenase (PDH) complex, a critical gatekeeper linking glycolysis to the TCA cycle.

Furthermore, LonP1 has emerged as a key mediator of cell stress responses, which is up-regulated in various cancers. As a result, it is a potential target for anti-cancer therapies. Our identification of small molecules that allosterically inhibit the ATPase activity of LonP1 holds promise for discovering and developing specific, high-affinity compounds for use as chemotherapeutic agents and valuable chemical probes for cancer treatment and biomedical research.

Research support:
NIH-NIGMS- 1 R01 GM136905-01, -01S1, -03S1, -03S2
Busch Foundation Grant

More to come.

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