Biological complexity: cells manage mitochondrial stress (Introduction)

by David Turell , Friday, October 18, 2019, 21:26 (1863 days ago) @ dhw

Special factors control mitochondrial stress:

https://www.sciencedaily.com/releases/2019/10/191018125506.htm

"Cells need powerhouses known as mitochondria to utilize the energy stored in our food. Most of the proteins required for this powerhouse function are encoded in the nucleus and transported into the mitochondria after they have been synthesized in the cytosol. Signal sequences are needed to allow the protein to enter the mitochondria. Once the protein has arrived there, the signal sequences are, however, removed.....Dr. Nora Vögtle of the Institute of Biochemistry and Molecular Biology of the University of Freiburg has discovered that errors in the removal of signal sequences lead to an aggregation of these proteins so that they clump together inside the mitochondria.

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"The aggregation observed by the researchers could cause the cell powerhouses to stop working, but all organisms require this activity for survival. To counteract these defects the cells execute what the researchers call a protective stress response, which enables mitochondria to maintain their key functions.

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"'Only through this mechanism could the mitochondria ensure cell survival by maintaining generation of energy under these stressful conditions. This completely novel principle in the stress response of cells, explains Vögtle, is probably the earliest reaction that has been detected up until now. She says, "That's the cell's first line of defense when stress appears in its powerhouses.'" (my bold)

From the paper:

"Summary
The mitochondrial proteome is built mainly by import of nuclear-encoded precursors, which are targeted mostly by cleavable presequences. Presequence processing upon import is essential for proteostasis and survival, but the consequences of dysfunctional protein maturation are unknown. We find that impaired presequence processing causes accumulation of precursors inside mitochondria that form aggregates, which escape degradation and unexpectedly do not cause cell death. Instead, cells survive via activation of a mitochondrial unfolded protein response (mtUPR)-like pathway that is triggered very early after precursor accumulation. In contrast to classical stress pathways, this immediate response maintains mitochondrial protein import, membrane potential, and translation through translocation of the nuclear HMG-box transcription factor Rox1 to mitochondria. Rox1 binds mtDNA and performs a TFAM-like function pivotal for transcription and translation. ( Mitochondrial transcription factor A, abbreviated as TFAM or mtTFA, is a protein that in humans is encoded by the TFAM gene.)
Induction of early mtUPR provides a reversible stress model to mechanistically dissect the initial steps in mtUPR pathways with the stressTFAM Rox1 as the first line of defense."

Comment: this complex mechanism had to be in place early to protect the mitochondria. Only design fits