Research

Key Highlights From the Lab.......

Lipid Homeostasis

We showed that a specific subpopulation of mitochondria controls lipid droplet dynamics. For the first time, we demonstrated the presence of two distinct mitochondrial populations in rat liver—cytoplasmic mitochondria and lipid droplet–associated mitochondria—where lipid droplet–associated mitochondria exhibit higher fatty acid oxidation, while cytoplasmic mitochondria display greater respiratory capacity; importantly, we established that disruption of this functional segregation contributes to NAFLD.

Mitochondrial Derived Vesicles

Mitochondria maintain cellular homeostasis through mitochondrial-derived vesicles (MDVs), yet their role in the mammalian liver has remained unclear. We demonstrated the in vitro generation of metabolically enriched MDVs from rat liver mitochondria and identified a novel TOMM70⁺ MDV subset that mediates inter-mitochondrial communication, revealing a new pathway linking mitochondrial quality control, stress adaptation, and metabolism.

Autophagy

We identified the Cvt autophagy proteins Atg19 and Ape1 as the physiological substrates of the methionine sulfoxide reductase Mxr2 in Saccharomyces cerevisiae. We showed that Mxr2 stabilizes immature Ape1 (via. Met17-dependent redox regulation) and Atg19, revealing a previously unrecognized link between oxidative control and the Cvt autophagy pathway.

Mitochondrial Biology Laboratory uses mammalian and yeast model systems to dissect the molecular mechanisms underlying mitochondrial retrograde signaling, redox homeostasis, and inter-organellar communication in health and disease. Using yeast as a powerful model for redox biology, we demonstrated that Mge1, an evolutionarily conserved nucleotide exchange factor of mitochondrial Hsp70, functions as an oxidative sensor and is reversibly regulated by methionine sulfoxide reductase, linking redox status to mitochondrial protein homeostasis.

Our work further established the critical role of methionine sulfoxide reductase in regulating the cytoplasm-to-vacuole targeting (Cvt) autophagy pathway and in modulating general autophagy through transcriptional control of Atg8. We have also shown that mitochondrial complex I–generated reactive oxygen species (ROS) act as signaling molecules to recruit the transcription factor STAT3 to mitochondria, thereby driving mitochondrial retrograde signaling.

More recently, we uncovered a novel connection between mitochondria and plasma membrane organization by demonstrating that the eisosomal protein Pil1 regulates mitochondrial morphology, dynamics, mitophagy, and cell death. In a key study, we identified a functionally distinct subpopulation of mitochondria that controls lipid droplet dynamics in rat liver, revealing the existence of cytoplasmic mitochondria and lipid droplet–associated mitochondria with specialized metabolic functions. While lipid droplet–associated mitochondria exhibit enhanced fatty acid oxidation, cytoplasmic mitochondria display higher respiratory capacity, and disruption of this functional segregation predisposes cells to metabolic disorders such as NAFLD.

Collectively, our studies highlight the remarkable plasticity of mitochondria and underscore their dynamic communication, cooperation, and signaling with other cellular organelles to preserve cellular homeostasis.

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