MOCB Seminar: "Energy Matters: Reprogramming mitochondrial transport in synaptic transmission"

Wednesday, May 18, 2022
12:00 p.m.
1103 Bioscience Research Building

Speaker: Dr. Zuhang Sheng (National Institute of Neurological Disorders and Stroke)

Title: "Energy Matters: Reprogramming mitochondrial transport and energy metabolism in synaptic transmission and CNS regeneration"

Abstract: Mitochondria are cellular power plants that generate energy in the form of ATP to power synaptic transmission and neuronal regeneration. Neurons are highly polarized cells consisting of complex dendritic arbors and a single long axon with extensive branches and terminals, thus facing exceptional challenges in maintaining energy homeostasis in distal axons and synapses. Only ~33% of presynaptic terminals retain mitochondria, and as such sustained synaptic activity is restricted within mitochondria-containing synapses. Therefore, revealing mechanisms for recruiting and retaining presynaptic mitochondria will advance our knowledge as how neurons sustain synaptic efficacy and plasticity. Brain injury triggers acute mitochondrial damage leading to local energy crisis, thus contributing to CNS regeneration failure and permanent neurological impairments. Thus, replacing damaged mitochondria with healthy ones will accelerate bioenergetic recovery, and thus meet increased energy demand for neuron survival and repair. Investigations into the regulation of mitochondrial trafficking and energy metabolism represent an important emerging area.

We previously identified syntaphilin (SNPH) as a static anchor for axonal mitochondria (Kang et al., Cell 2008). In the presentation, I will discuss a new mechanistic crosstalk between presynaptic energy sensing and mitochondrial anchoring. Sustained synaptic activity induces presynaptic energy deficits that could be effectively recovered by recruiting mitochondria through an interplay between AMPK-PAK energy signaling and SNPH-mediated mitochondrial anchoring on presynaptic F-actin, thus maintaining prolonged synaptic efficacy (Li et al., Nature Metabolism 2020). I will also discuss how brain injury trigger acute mitochondrial damage leading to local energy crisis, and how enhancing mitochondrial transport rescues energy deficits in injured axons, thus facilitating CNS regeneration and functional recovery (Zhou et al., JCB 2016; Han et al., Cell Metabolism 2020). We further reveal an intrinsic signaling pathway that replaces damaged mitochondria with healthy ones in response to axonal injury, thus supplying energy for regeneration (Huang et al., Current Biology 2021). Axonal energetic metabolism could also be boosted by a transcellular signaling pathway between glial cells and neurons (Chamberlain et al., Neuron 2021). These studies provide new targets for reprogramming mitochondrial transport and energy metabolism to facilitate CNS regeneration (Supported by the Intramural Research Program of NINDS, NIH).

Bio: Dr. Sheng is an expert in the area of organelle transport and membrane trafficking with a focus on the mechanisms regulating axonal transport of mitochondria, endocytic organelles, and synaptic cargo and their impact on axonal homeostasis, synaptic function and neurodegeneration.

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