Qian Cai
Associate Professor
Department: Cell Biology & Neuroscience
Phone: 1.8484451633
Email: mailto:cai@dls.rutgers.edu
Rutgers University
Nelson Labs, Room B231
Piscataway, NJ 08854
Key Words: Autophagy-lysosomal regulation in neurodevelopment and neurodegeneration

Autophagy is a key homeostatic process whereby autophagosomes engulf damaged cytoplasmic components, misfolded proteins, and dysfunctional organelles for lysosomal degradation. In neurons, autophagosomes are predominantly formed in distal axons and nerve terminals and undergo robust retrograde transport toward the soma where mature lysosomes are mainly located. The autophagy-lysosomal pathway is essential for the maintenance of cellular homeostasis. Defects within this pathway have been implicated in a growing number of neurological disorders.

Mitochondria are essential organelles for neuronal function and survival. Dysfunctional mitochondria not only produce energy with less efficiency, but also release harmful reactive oxygen species and initiate apoptotic signaling cascades, which have been linked to the pathogenesis of a variety of neurodegenerative diseases. Mitophagy, the selective autophagic removal of damaged mitochondria, is a key cellular pathway for mitochondrial quality control in neurons.

The focus of our research is to elucidate the molecular and cellular mechanisms regulating the autophagy-lysosomal system and its impact on neuronal homeostasis and axonal degeneration. We are particularly interested in addressing the following questions: (1) What are the mechanisms regulating axonal transport, membrane trafficking, and autophagy-lysosomal function? (2) How is mitochondrial quality controlled in heathy and diseased neurons? (3) How is the endolysosomal system involved in the regulation of neuronal signaling? (4) How do defects in these mechanisms contribute to neurodegeneration? (5) What are the mechanisms regulating neuronal morphogenesis and synapse formation through the autophagy-lysosomal pathway?

Our study provides the evidence of dynamic and spatial Parkin-mediated mitophagy in eliminating depolarized mitochondria in live neurons. We reveal that inadequate mitophagy capacity contributes to mitochondrial defects in Alzheimer’s disease brains. Our long-term goal is to elucidate the cellular mechanisms for proper turnover of defective mitochondria through mitophagy and clearance of protein aggregates by enhancing autophagy-lysosomal function. We will evaluate if up-regulation of this system ameliorates neuropathology and attenuates behavioral abnormalities associated with major neurodegenerative diseases. The advance in our understanding of these mechanisms will provide a basis that could lead to the development of novel protective and therapeutic approaches to overcome these neurological disorders.