Implications of mitochondrial network organization in mitochondrial stress signalling in NARP cybrid and Rho0 cells

Abstract

Mitochondrial dysfunctions lead to the generation of signalling mediators that influence the fate of that organelle. Mitochondrial dynamics and their positioning within the cell are important elements of mitochondria-nucleus communication. The aim of this project was to examine whether mitochondrial shape, distribution and fusion/fission proteins are involved in the mitochondrial stress response in a cellular model subjected to specifically designed chronic mitochondrial stress: WT human osteosarcoma cells as controls, NARP cybrid cells as mild chronic stress and Rho0 as severe chronic stress. We characterized mitochondrial distribution in these cells using confocal microscopy and evaluated the level of proteins directly involved in the mitochondrial dynamics and their regulation. We found that the organization of mitochondria within the cell is correlated with changes in the levels of proteins involved in mitochondrial dynamics and proteins responsible for regulation of this process. Induction of the autophagy/mitophagy process, which is crucial for cellular homeostasis under stress conditions was also shown. It seems that mitochondrial shape and organization within the cell are implicated in retrograde signalling in chronic mitochondrial stress.