Researchers from Ruhr University Bochum have revealed new insights into the function of mitochondria in the nervous and immune systems.
Mitochondria are known primarily as the powerhouse of the cell. However, these cellular organelles are required for more than just providing energy, according to researchers from the Faculty of Medicine at Ruhr University Bochum in Germany. A research group led by Professor Konstanze Winklhofer has discovered that mitochondria have a vital role in signal transduction in innate immune pathways and immune systems.
Mitochondria are responsible for regulating the signalling pathway that helps the body to eliminate pathogens. However, they can cause damage through inflammation upon overactivation.
The findings have been published in the EMBO Journal.
Mitochondria can protect against viruses in immune systems
Certain cytokines and intracellular pathogens, such as viruses and some bacteria, activate the transcription factor NF-κB> These regulate the expression of various genes in the body.
“Depending on the stimulus and the cell type, NF-κB activation results in protection from cell death and increased synthesis of proteins required for the elimination of bacteria or viruses,” explained Winklhofer.
However, the protective pathway can cause chronic inflammation if it is exposed to excessive and prolonged activation.
“Hence, a fine-tuned regulation of these signalling processes is of great medical relevance, in order to prevent pathophysiological conditions caused by either inefficient or overshooting NF-κB activation,” added Winklhofer.
The findings of the study have revealed that mitochondria play a crucial role in the regulation of the NF-κB signalling pathway. Within minutes of pathway activation, a signalling platform assembles at the outer mitochondrial membrane, resulting in the activation of NF-κB.
“This allows signal amplification, based on the large surface of mitochondria,” said Winklhofer.
“Moreover, mitochondria have another capacity that qualifies them as organelles for signal transduction: they are mobile and can dock onto motor proteins in the cell.”
The researchers established that mitochondria are responsible for escorting the activated transcription factor NF-κB to the nuclear membrane. This facilitates the translocation of NF-κB into the nucleus.
However, mitochondria are responsible for more than the efficient activation of the NF-κB signalling pathway. They also contribute to the deactivation and regulation of the signal. This is achieved by an enzyme in the outer mitochondrial membrane, which counteracts ubiquitination, a posttranslational modification essential for NF-κB activation.
Why are Parkinson’s disease patients more vulnerable to infection?
The researchers identified two genes that were causally linked to Parkinson’s disease which were involved in the mitochondrial regulation of the NF-κB signalling pathway: PINK1 and Parkin.
“Our findings explain why mutations resulting in a loss of PINK1 or Parkin function promote neuronal cell death under stress conditions,” said Winklhofer.
“Remarkably, our findings show that Parkinson’s disease patients with mutations in the PINK1 or Parkin gene show an increased vulnerability to various infections caused by intracellular pathogens. Thus, our study also helps to gain a better understanding of the interfaces between the nervous and immune systems,” he concluded.
