Effects of general anesthetics on mitochondrial cellular distribution

NIH RePORTER · NIH · K08 · $194,940 · view on reporter.nih.gov ↗

Abstract

Project Summary: The neuron is one of the highest energy-consuming cells within the body. It requires energy to maintain complex electrical gradients for neuron activation and signal transduction via synaptic vesicle release. The mitochondria are critical to efficiently create energy and their location within the cell is tightly regulated through the use of motor protein complexes kinesin (anterograde) and dynein (retrograde). General anesthetics have been shown to bind to kinesin motor proteins and decrease their processivity. However, the effect of that binding on cellular machinery, energy homeostasis and anesthetic sensitivity has not been studied. This project explores the affect general anesthetics have on mitochondrial location, and by extension energy, using both the zebrafish in vivo model organism and primary neural cell culture. I define mitochondrial movement alterations when exposed to different anesthetics. Next, I define zebrafish larvae and neural cells within two mitochondrial transport, kif5Aa and actr10, as well as how that movement is altered in response to different anesthetics. Finally, I will determine how changing the mitochondrial distribution within neurons affects whole organism behavior by testing for changes in sensitivity to anesthetics within zebrafish larvae. Completing this project will enhance my skills in neurobiology, mitochondrial biology, advanced statistics and programming. With these skills I will be able to create a unique niche within the field of anesthesia. This project will also give me to preliminary data to launch as an independent investigator and write an R01.

Key facts

NIH application ID
10887176
Project number
1K08GM149981-01A1
Recipient
UNIVERSITY OF PENNSYLVANIA
Principal Investigator
Victoria Marie Bedell
Activity code
K08
Funding institute
NIH
Fiscal year
2024
Award amount
$194,940
Award type
1
Project period
2024-05-01 → 2024-10-31