scholarly journals Mitochondria Form Contact Sites with the Nucleus to Couple Pro-Survival Retrograde Response

2019 ◽  
Author(s):  
Radha Desai ◽  
Daniel A. East ◽  
Liana Hardy ◽  
James Crosby ◽  
Manuel Rigon ◽  
...  
Keyword(s):  
Contact Sites ◽  
Retrograde Response

scholarly journals Mitochondria form contact sites with the nucleus to couple prosurvival retrograde response

2020 ◽  
Vol 6 (51) ◽  
pp. eabc9955 ◽  
Author(s):  
Radha Desai ◽  
Daniel A. East ◽  
Liana Hardy ◽  
Danilo Faccenda ◽  
Manuel Rigon ◽  
...  
Keyword(s):  
Translocator Protein ◽  
Nuclear Factor ◽  
Kappa Light Chain ◽  
Adaptation To Stress ◽  
Cellular Adaptation ◽  
Contact Sites ◽  
Anchoring Protein ◽  
Light Chain Enhancer ◽  
Kinase A ◽  
Retrograde Response

Mitochondria drive cellular adaptation to stress by retro-communicating with the nucleus. This process is known as mitochondrial retrograde response (MRR) and is induced by mitochondrial dysfunction. MRR results in the nuclear stabilization of prosurvival transcription factors such as the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB). Here, we demonstrate that MRR is facilitated by contact sites between mitochondria and the nucleus. The translocator protein (TSPO) by preventing the mitophagy-mediated segregation o mitochonria is required for this interaction. The complex formed by TSPO with the protein kinase A (PKA), via the A-kinase anchoring protein acyl-CoA binding domain containing 3 (ACBD3), established the tethering. The latter allows for cholesterol redistribution of cholesterol in the nucleus to sustain the prosurvival response by blocking NF-κB deacetylation. This work proposes a previously unidentified paradigm in MRR: the formation of contact sites between mitochondria and nucleus to aid communication.

scholarly journals Mitochondria form contact sites with the nucleus to couple pro-survival retrograde response

2018 ◽  
Author(s):  
Radha Desai ◽  
Daniel A East ◽  
Liana Hardy ◽  
James Crosby ◽  
Manuel Rigon ◽  
...  
Keyword(s):  
Cell Signalling ◽  
Translocator Protein ◽  
Nuclear Factor ◽  
Mitochondrial Network ◽  
New Paradigm ◽  
Mitochondrial Dysfunctions ◽  
Contact Sites ◽  
Anchoring Protein ◽  
Light Chain Enhancer ◽  
Retrograde Response

AbstractMitochondria drive cellular adaptation to stress by retro-communicating with the nucleus. This process is known as Mitochondrial Retrograde Response (MRR) and is induced by mitochondrial dysfunctions which perturb cell signalling. MRR results in the nuclear stabilization and activation of pro-survival transcription factors such as the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB). Here we demonstrate that MRR is facilitated by the formation of contact sites between mitochondria and the nucleus which establish microdomains of communication between the two organelles. The 18kD Translocator Protein (TSPO), which de-ubiquitylates and stabilizes the mitochondrial network preventing its mitophagy-mediated segregation, is required for this interaction. The tethering TSPO enacts is mediated by the complex formed with the Protein Kinase A via the A-kinase anchoring protein Acyl-CoA Binding Domain Containing 3 (ACBD3) and allows the redistribution of cholesterol which sustains the pro-survival response by blocking NF-kB de-acetylation. This work proposes a new paradigm in the mitochondrial retro-communication by revealing the existence of contact sites between mitochondrial and the nucleus and a signalling role for cholesterol.

Structure of contact sites between the outer and inner mitochondrial membranes investigated by HVEM tomography

1996 ◽  
Vol 54 ◽  
pp. 966-967
Author(s):  
C.A. Mannella ◽  
K.F. Buttle ◽  
K.A. O‘Farrell ◽  
A. Leith ◽  
M. Marko
Keyword(s):  
Liver Mitochondrion ◽  
Adenine Nucleotide ◽  
Protein Complexes ◽  
Mitochondrial Membranes ◽  
Electron Microscopic ◽  
Contact Sites ◽  
Transmission Electron ◽  
Precursor Proteins ◽  
Membrane Contacts ◽  
And Function

Early transmission electron microscopy of plastic-embedded, thin-sectioned mitochondria indicated that there are numerous junctions between the outer and inner membranes of this organelle. More recent studies have suggested that the mitochondrial membrane contacts may be the site of protein complexes engaged in specialized functions, e.g., import of mitochondrial precursor proteins, adenine nucleotide channeling, and even intermembrane signalling. It has been suggested that the intermembrane contacts may be sites of membrane fusion involving non-bilayer lipid domains in the two membranes. However, despite growing interest in the nature and function of intramitochondrial contact sites, little is known about their structure.We are using electron microscopic tomography with the Albany HVEM to determine the internal organization of mitochondria. We have reconstructed a 0.6-μm section through an isolated, plasticembedded rat-liver mitochondrion by combining 123 projections collected by tilting (+/- 70°) around two perpendicular tilt axes. The resulting 3-D image has confirmed the basic inner-membrane organization inferred from lower-resolution reconstructions obtained from single-axis tomography.

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