Broken mitochondria use 'eat me' proteins to summon their executioners
When mitochondria become damaged, they avoid causing further problems by signaling cellular proteins to degrade them. In a paper publishing April 11, 2019, in the journal Developmental Cell, scientists in Norway report that they have discovered how the cells trigger this process, which is called mitophagy. In cells with broken mitochondria, two proteins -- NIPSNAP 1 and NIPSNAP 2 -- accumulate on the mitochondrial surface, functioning as "eat me" signals, recruiting the cellular machinery that will destroy them.
NIPSNAP 1 and 2 are normally found inside healthy mitochondria, although their function inside the cell is unknown. "When a cell's respiration chain is disrupted, and the mitochondria are damaged, import of these proteins into the matrix and inner membrane space of the mitochondria is interrupted," says senior author Anne Simonsen, a professor at the Department of Molecular Medicine at the Institute of Basic Medical Sciences of the University of Oslo. "In that case, the import system does not function and they remain bound to the surface of the damaged mitochondria signaling for mitophagy."
In this study, the researchers studied human HeLa cells where both NIPSNAP1 and NIPSNAP 2 function were eliminated. "When we do that, these cells cannot clear the mitochondria after damage," says Simonsen. However, in cells with functional NIPSNAP proteins, when mitophagy was induced through the addition of a chemical disruptor, they observed that the NIPSNAP proteins act in concert with the PINK and PARKIN proteins, proteins already known to have a role in triggering autophagy and to have a role in Parkinson's Disease.
PARKIN labels cells with ubiquitin, a small protein that directs the cells towards degradation. "Ubiquitin is the classical signal to recruit autophagy," says co-author Terje Johansen, of the University of Tromsø -- The Arctic University of Norway. "What we saw is that in addition to ubiquitin, NIPSNAP proteins are required to recruit autophagy proteins; they are not targeted to the mitochondria unless these NIPSNAP proteins are found on the surface."
The team showed this finding has important physiological implications in vivo by investigating the NIPSNAP/PINK/PARKIN mechanism in a zebrafish animal model. They compared wild-type zebrafish and a fish line with reduced NIPSNAP1 protein abundance.
"We see that the mutant fish lacking adequate functional NIPSNAP1 are not able to move as the wild-type fish," says Simonsen. They have a Parkinsonian-like phenotype with reduced numbers of dopaminergic neurons. However, they could rescue this locomotion defect by adding L-dopa, the same compound used to treat human Parkinson's Disease, to the water.
Even more dramatically, animals entirely lacking NIPSNAP1 protein died within five days. "Clearly, clearance of mitochondria is important for the health of these dopaminergic neurons. That is particularly important since neurons generally cannot divide," says Johansen.
As evolutionarily conserved proteins, NIPSNAP proteins are found throughout the animal kingdom, including humans.
This work was partly funded by the Research Council of Norway, the Norwegian Cancer Society, and the Parkinson's Disease Foundation.
News Source : www.sciencedaily.com
Journal Reference:
Yakubu Princely Abudu, Serhiy Pankiv, Benan John Mathai, Alf Håkon Lystad, Christian Bindesbøll, Hanne Britt Brenne, Matthew Yoke Wui Ng, Bernd Thiede, Ai Yamamoto, Thaddaeus Mutugi Nthiga, Trond Lamark, Camila V. Esguerra, Terje Johansen, Anne Simonsen. NIPSNAP1 and NIPSNAP2 Act as 'Eat Me' Signals for Mitophagy. Developmental Cell, 2019; DOI: 10.1016/j.devcel.2019.03.013
Researchers can finally modify plant mitochondrial DNA
Rice in field (stock image). Credit: © orijinal_x / Adobe Stock
Researchers have edited plant mitochondrial DNA for the first time, which could lead to a more secure food supply. Nuclear DNA was first edited in the early 1970s, chloroplast DNA was first edited in 1988, and animal mitochondrial DNA was edited in 2008. However, no tool previously successfully edited plant mitochondrial DNA. Researchers used their technique to create four new lines of rice and three new lines of rapeseed (canola).
Nuclear DNA was first edited in the early 1970s, chloroplast DNA was first edited in 1988, and animal mitochondrial DNA was edited in 2008. However, no tool previously successfully edited plant mitochondrial DNA.
Researchers used their technique to create four new lines of rice and three new lines of rapeseed (canola).
"We knew we were successful when we saw that the rice plant was more polite -- it had a deep bow," said Associate Professor Shin-ichi Arimura, joking about how a fertile rice plant bends under the weight of heavy seeds.
Arimura is an expert in plant molecular genetics at the University of Tokyo and led the research team, whose results were published in Nature Plants. Collaborators at Tohoku University and Tamagawa University also contributed to the research.
News source: www.sciencedaily.com
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10th Anniversary of Targeting Mitochondria Congress The World Mitochondria Society has the pleasure to announce the 10th Anniversary of Targeting Mitochondria Congress, which will be held in Berlin, Germany, on October 27th – 29th, 2019. To know more about the Congress, please visit the Home page here |
Program of Targeting Mitochondria 2019 Congress/Speakers/Early Registration/May 21, 2019
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Mitochondrial Copper Toxicity with a Focus on Wilson Disease
Selective segregation of mitochondria in asymmetric stem cell divisions
Cardiac glycosides modulate neuroblastoma stem cell survival by dysfunctional mitophagy
Mitochondria, as central regulators of neural stem cell fate
The cellular stress protein MNRR1/CHCHD2 and mitochondrial disease
Cannabinoids and skin: The "c(ut)annabinoid" system as a novel player in regulating cutaneous mitochondrial biology
Mitochondrial reactive oxygen species in heart failure
Caffeine from four cups of coffee protects the heart with the help of mitochondria
A new study shows that a caffeine concentration equivalent to four cups of coffee promotes the movement of a regulatory protein into mitochondria, enhancing their function and protecting cardiovascular cells from damage.
Caffeine consumption has been associated with lower risks for multiple diseases, including type II diabetes, heart disease, and stroke, but the mechanism underlying these protective effects has been unclear. A new study now shows that caffeine promotes the movement of a regulatory protein into mitochondria, enhancing their function and protecting cardiovascular cells from damage. The work, publishing 21 June in the open access journal PLOS Biology, by Judith Haendeler and Joachim Altschmied of the Medical Faculty, Heinrich-Heine-University and the IUF-Leibniz Research Institute for Environmental Medicine in Duesseldorf, Germany, and colleagues, found that the protective effect was reached at a concentration equivalent to consumption of four cups of coffee, suggesting the effect may be physiologically relevant.
News source: https://www.sciencedaily.com/releases/2018/06/180621141008.htm
PLOS. "Caffeine from four cups of coffee protects the heart with the help of mitochondria." ScienceDaily. ScienceDaily, 21 June 2018. <www.sciencedaily.com/releases/2018/06/180621141008.htm>.
Marvin Edeas - A Pilot Study - Microbiota Quality and Mitochondrial Activity Link with Occurrence of Muscle Cramps ...
Marvin Edeas explains Microbiota Quality and Mitochondrial Activity Link with Occurrence of Muscle Cramps in Hemodialysis Patients using Citrate Dialysate: A Pilot Study
Authors: Pierre-Yves Durand, Carole Nicco, Dedier Serteyn, David Attaf, Marvin Edeas
BACKGROUND/AIMS:
Hemodialysis-associated muscle cramp (HAMC) is a common complication under citrate dialysate (CD) occurring in 30% of cases. Our objectives were to assess the gut microbiota quality, mitochondrial activity, and to investigate their possible relationship with HAMC.
METHODS:
Ten end-stage renal disease patients (78.9 ± 2.1 years) treated by hemodialysis (HD) with CD were enrolled and then classified according to the frequency of HAMCs: "frequent HAMCs group" (n = 5) and "absence of HAMCs group" (n = 5). Gut microbiota quality, mitochondrial activity, and some markers of oxidative stress (OS) were investigated.
RESULTS:
In patients with cramps, gut microbiota diversity seemed lower and some genera including Helicobacter, Lachnospira, Roseburia, and Haemophilus seemed over-expressed, a significant increase of citratemia and significant lowering mitochondrial function were observed. No difference was observed on the OS markers.
CONCLUSION:
This first clinical study revealed a possible dysbiosis of microbiota and a mitochondrial dysfunction into HD patients with cramps under CD compared to patients without cramp.
© 2018 S. Karger AG, Basel.
