Cell biology: How Cellular Powerhouses Call for Help When Under Stress
Published:15 Nov.2023    Source:Goethe University Frankfurt
How closely the cell and the mitochondrion work together in human cells today is what a team of researchers led by Dr. Christian Münch of Goethe University Frankfurt is investigating. They have now discovered how the mitochondrion calls for help from the cell when it is under stress. A certain type of mitochondrial stress is caused by misfolded proteins that are not quickly degraded and accumulate in the mitochondrion. The consequences for both the mitochondrion and the cell are dramatic: Misfolded proteins can, for example, disrupt energy production or lead to the formation of larger amounts of reactive oxygen compounds, which attack the mitochondrial DNA and generate further misfolded proteins. In addition, misfolded proteins can destabilize the mitochondrial membranes, releasing signal substances from the mitochondrion that activate apoptosis, the cell's self-destruction program.
The mitochondrion responds to the stress by producing more chaperones (folding assistants) to fold the proteins in order to reduce the misfolding, as well as protein shredding units that degrade the misfolded proteins. The researchers from Goethe University Frankfurt artificially triggered misfolding stress in the mitochondria of cultured human cells and analyzed the result. The result is that the mitochondria send two chemical signals to the cell when protein misfolding stress occurs: They release reactive oxygen compounds and block the import of protein precursors, which are produced in the cell and are only folded into their functional shape inside the mitochondrion, causing these precursors to accumulate in the cell.
As biochemist Münch explains, "It was very exciting to discover how the two mitochondrial stress signals are combined into one signal in the cell, which then triggers the cell's response to mitochondrial stress. Moreover, in this complex process, which is essentially driven by tiny local changes in concentration, the stress signaling pathways of the cell and the mitochondrion dovetail very elegantly with each other -- like the cogs in a clockwork."