Mitochondrial transport and quality control in neurons - we seek to understand the regulatory mechanisms that control the movements of mitochondria in cells

The National Institute of General Medical Sciences awarded The Leland Stanford Junior University $423,500 for a Project Grant (R35GM161519) on April 1, 2026, to investigate the regulatory mechanisms controlling mitochondrial transport and quality control in neurons. The work performs at Stanford's Palo Alto, California campus through January 31, 2031.

The research focuses on understanding how mitochondria move and undergo fission and fusion within neuronal cells, particularly to supply mitochondria to the distant axonal and dendritic extremities where defects can trigger peripheral neuropathies and neuronal degeneration. The award builds on prior identification of a protein complex including Milton, Miro, and kinesin-1 heavy chain that drives anterograde mitochondrial transport. The funded work will examine how multiple mitochondrial and cytosolic signals converge to regulate mitochondrial motility and quality, addressing the integration of cellular signaling pathways that enable proper mitochondrial distribution across neuronal compartments and permit neuronal response to stress and activity changes.

The funding falls under the NIGMS Biomedical Research and Research Training program (CFDA 93.859), which supports basic research advancing understanding of biological processes and laying foundations for disease diagnosis, treatment, and prevention.

Mitochondria move and undergo fission and fusion in all eukaryotic cells, but the need to supply mitochondria to the far-flung extremities of neurons creates a particular urgency for mitochondrial transport in neurons. Defects in mitochondrial movements can give rise to peripheral neuropathies and degeneration. We and our colleagues have identified a protein complex that includes milton, miro, and the kinesin-1 heavy chain (KHC) and have shown that this complex is essential for the anterograde ((+)-end directed) transport of mitochondria in neurons. We have determined that multiple mitochondrial inside-out and cytosolic signals converge on miro to regulate mitochondrial motility. We now propose to further our understanding of the integration of cellular signals that influence mitochondrial motility and quality in neurons. These signaling pathways are crucial to the ability of mitochondria to properly distribute themselves within neuronal compartments and to permit neurons to respond to stresses and changes in activity.