scholarly journals ADP-ribosylation of mitochondrial proteins is mediated by Neuralized-like protein 4 (NEURL4)

2020 ◽  
Author(s):  
Maria Dafne Cardamone ◽  
Yuan Gao ◽  
Julian Kwan ◽  
Vanessa Hayashi ◽  
Megan Sheeran ◽  
...  

ADP-ribosylation is a reversible post-translational modification where an ADP-ribose moiety is covalently attached to amino acid side-chains of target proteins either as mono-ADP-ribose (MARylation or MAR) or poly-ADP-ribose chains (PARylation or PAR) by a class of enzymes called ADP-ribosyltransferases (ARTs). Although ADP-ribosylation is best known for its nuclear roles, ADP-ribosylation of extra nuclear proteins is increasingly recognized as a key regulatory strategy across cellular compartments. ADP-ribosylation of mitochondrial proteins, in particular, has been widely reported, even though the extent to which ADP-ribosylation of specific proteins regulates mitochondrial functions is unclear and the exact nature of mitochondrial ART enzymes is debated.Here, we have identified Neuralized-like protein 4 (NEURL4) as a mitochondrial ART enzyme and profiled the NEURL4-dependent ADP-ribosylome in mitochondrial extracts from Hela cells by LC-MS/MS, using isobaric tandem mass tag (TMT) labeling for relative quantification. Comparison of WT and NEURL4-KO cells generated by CRISPR/Cas9 genome editing revealed that most ART activity associated with mitochondria is lost in absence of NEURL4. Putative NEURL4 targets include numerous mitochondrial proteins previously shown to be ADP-ribosylated. In particular, we show that NEURL4 enzymatic activity is required for the regulation of mtDNA integrity via poly-ADP-ribosylation of mitochondrial specific Ligase III (mtLIG3), the rate-limiting enzyme for mitochondrial DNA (mtDNA) Base Excision Repair (BER).Collectively, our studies reveal that NEURL4 acts as the main mitochondrial ART enzyme under physiological conditions and provide novel insights in the regulation of mitochondria homeostasis through ADP-ribosylation.

1992 ◽  
Vol 102 (4) ◽  
pp. 663-670
Author(s):  
F.R. Althaus

In DNA excision repair of mammalian cells, the processing of ADP-ribose by the poly ADP-ribosylation system of chromatin is stimulated several thousand-fold. Most of this turnover is associated with the automodification reaction of the nuclear enzyme poly(ADP-ribose) polymerase and the degradation of polymerase-bound polymers by the enzyme poly(ADP-ribose) glycohydrolase. The automodification cycle catalyzes a temporary dissociation from and reassociation of histones with DNA. It is proposed that this mechanism, termed “histone shuttle”, may guide specific proteins to sites of repair. In addition, histone shuttling driven by the poly ADP-ribosylation system seems to be involved in nucleosomal unfolding of chromatin in DNA excision repair.


2013 ◽  
Vol 2013 ◽  
pp. 1-17 ◽  
Author(s):  
Sanjeev K. Anand ◽  
Suresh K. Tikoo

Mitochondria are multifunctional organelles with diverse roles including energy production and distribution, apoptosis, eliciting host immune response, and causing diseases and aging. Mitochondria-mediated immune responses might be an evolutionary adaptation by which mitochondria might have prevented the entry of invading microorganisms thus establishing them as an integral part of the cell. This makes them a target for all the invading pathogens including viruses. Viruses either induce or inhibit various mitochondrial processes in a highly specific manner so that they can replicate and produce progeny. Some viruses encode the Bcl2 homologues to counter the proapoptotic functions of the cellular and mitochondrial proteins. Others modulate the permeability transition pore and either prevent or induce the release of the apoptotic proteins from the mitochondria. Viruses like Herpes simplex virus 1 deplete the host mitochondrial DNA and some, like human immunodeficiency virus, hijack the host mitochondrial proteins to function fully inside the host cell. All these processes involve the participation of cellular proteins, mitochondrial proteins, and virus specific proteins. This review will summarize the strategies employed by viruses to utilize cellular mitochondria for successful multiplication and production of progeny virus.


2004 ◽  
Vol 32 (Supplement) ◽  
pp. A21 ◽  
Author(s):  
Yi-Chen Lai ◽  
Y Chen ◽  
X Zhang ◽  
P M Kochanek ◽  
P D. Nathaniel ◽  
...  

Cells ◽  
2019 ◽  
Vol 8 (8) ◽  
pp. 890 ◽  
Author(s):  
Hopp ◽  
Grüter ◽  
Hottiger

Cells constantly adapt their metabolic pathways to meet their energy needs and respond to nutrient availability. During the last two decades, it has become increasingly clear that NAD+, a coenzyme in redox reactions, also mediates several ubiquitous cell signaling processes. Protein ADP-ribosylation is a post-translational modification that uses NAD+ as a substrate and is best known as part of the genotoxic stress response. However, there is increasing evidence that NAD+-dependent ADP-ribosylation regulates other cellular processes, including metabolic pathways. In this review, we will describe the compartmentalized regulation of NAD+ biosynthesis, consumption, and regeneration with a particular focus on the role of ADP-ribosylation in the regulation of glucose metabolism in different cellular compartments.


2020 ◽  
Author(s):  
Qian Chen ◽  
Chunjing Bian ◽  
Xin Wang ◽  
Xiuhua Liu ◽  
Muzaffer Ahmad Kassab ◽  
...  

2005 ◽  
Vol 25 (1_suppl) ◽  
pp. S447-S447
Author(s):  
Yi-Chen Lai ◽  
Yamming Chen ◽  
Xiaopeng Zhang ◽  
Paula D Nathaniel ◽  
Fengli Guo ◽  
...  

2002 ◽  
Vol 75 (5) ◽  
pp. 507 ◽  
Author(s):  
Katherine J. Kim ◽  
Indraneel Chakrabarty ◽  
Guang-Zhi Li ◽  
Sabine Grösch ◽  
Bernd Kaina ◽  
...  

Author(s):  
Richarda de Voer ◽  
Paul W Doetsch ◽  
Roland Kuiper ◽  
Barbara Rivera

2018 ◽  
Vol 482 (1) ◽  
pp. 96-100
Author(s):  
E. Belousova ◽  
◽  
M. Kutuzov ◽  
P. Ivankina ◽  
A. Ishchenko ◽  
...  

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