Welcome to the Suzuki Lab
Integrative Mitochondrial Biology
Our lab aims at understanding integrated mechanisms regulating mitochondrial energy metabolism, mitochondrial proteostasis and mitochondrial gene expression, and how cellular stressors impact these processes. Three main lines of research focus on:
Physiological roles of LonP1. LonP1 is a mitochondrial ATP-dependent protease that plays a crucial role in mitochondrial and cellular homeostasis. Recent studies have indicated a central role for LonP1 in integrating mitochondrial metabolism, energetics and proteostasis. Its physiological functions include- degrading abnormal proteins and key rate-limiting proteins, acting as a molecular chaperone; and ensuring the maintenance and expression of mitochondrial DNA.
LonP1 dysfunction in rare diseases. LonP1 dysfunction has been associated with multiple rare and ultra-rare disorders and diseases including classical mitochondrial disease and CODAS syndrome which is a multi-system developmental disorder characterized by cerebral, ocular, dental auricular and skeletal anomalies.
Post-translational regulation of mitochondrial transcription factor A (TFAM). TFAM is essential for activating the transcription of mitochondria DNA (mtDNA), and also for mtDNA maintenance and transmission. We have shown that TFAM is post-translationally modified by acetylation and phosphorylation and LonP1-dependent proteolysis, thereby regulating mitochondrial transcription. We are making strides in understanding physiological importance of these modifications in mitochondrial energy metabolism.
Our lab employs biochemical and molecular cell biological techniques using purified proteins and cultured cells, respectively. Advanced imaging techniques such as single-molecule fluorescence in situ hybridization (smFISH) to study synthesis, half-lives and spatial distribution of RNA transcripts, and click chemistry applications to determine the biogenesis, turnover and localization of newly synthesized proteins.
We utilize and have developed several experimental systems and models including primary patient fibroblasts and induced pluripotent stem cells (iPSCs) derived from individuals with rare mitochondrial diseases caused by mutations in the LONP1 gene, encoding the mitochondrial LonP1 protease.
We have further differentiated the patient-derived iPSCs into neural and cardiomyocyte cell lines as organ system models to elucidate the mechanistic cause of the diversity of disease phenotypes associated with LonP1 mutations- from classic ragged-red fiber pathology to neurodegeneration.