Neurons are generally considered as terminally differentiated cells with very limited or no capacity to adapt their energy metabolism to challenging conditions. For some neurological diseases, there is ample evidence that mitochondrial dysfunction can be tolerated for lengthy periods of time. The researchers, therefore, asked the question whether degenerating neurons may activate a program of metabolic resilience.
“We devised an innovative approach to purify degenerating neurons from the mouse brain and to analyze the global protein content, the proteome, of these neurons. Unexpectedly, the proteomic data showed the existence of a precisely coordinated, neuron-specific metabolic program that becomes activated in response to mitochondrial dysfunction”, says Nils-Göran Larsson, the corresponding author of the study and professor at the Department of Medical Biochemistry and Biophysics at Karolinska Institutet.