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.
Highlights
Impairment of mitochondrial functioning routinely generates signalling mediators that may determine the fate of this organelle and stress signals can stimulate cellular adaptation
We previously showed that mitochondria in WT osteosarcoma cells exhibit an elongated shape and form tubular network-like structures throughout the cell body, whereas in NARP cells, the shape of the mitochondria varies from tubular to rounded to punctate, and the mitochondria are more fragmented in the peripheral cell body
Based on our previous findings showing that point mutations in subunit 6 of ATP synthase in mitochondrial DNA (mtDNA) cause chronic mitochondrial stress, manifested in increased levels of ROS, elevation of cytoplasmic calcium ion levels, and alterations of the mitochondrial membrane potential and mitochondrial network organization within the cell[10,11,12], we concluded that mitochondrial shape and the mitochondrial distribution might be involved in the modulation of mitochondrial stress signalling pathways
Summary
Impairment of mitochondrial functioning routinely generates signalling mediators that may determine the fate of this organelle and stress signals can stimulate cellular adaptation. Loss of the mitochondrial fission-fusion balance is associated with many pathological processes, including mitochondrial stress, cellular senescence, and neuronal injury, as well as a number of diseases[9]. All this study show that chronic mitochondrial stress caused by mtDNA point mutation-NARP and loss of mtDNA - Rho[0], results in induction of mitochondrial biogenesis by triggering distinct adaptive changes in the profile of mitochondrial proteins and their regulatory transcription factors irrespective of nuclear genome. Because the mitochondrial morphology and fission/fusion processes are elements of quality control pathways and are implicated in the removal of damaged mitochondria through the autophagy pathway, we investigated the presence of autophagy in NARP and Rho[0] cells as well
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
