Poly(ADP-ribose) polymerases as modulators of mitochondrial activity

Bai, Péter; Nagy, L; Fodor, Tamás; Liaudet, Lucas; Pacher, Pál

doi:10.1016/j.tem.2014.11.003

Cited by 100 publications

(78 citation statements)

References 89 publications

(168 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…PARP-1 overactivation blunts mitochondrial activity through several parallel pathways (for comprehensive review see [8,42]): 1) inhibition of mitotropic transcription factors (e.g. SIRT1) [5,43], 2) induction of transcription factors that suppress mitochondrial activity (e.g.…”

Section: Mitochondrial Dysfunctionmentioning

confidence: 99%

“…HIFs) [44,45], 3) inhibiting mitochondrial membrane and membrane-associated enzymes (e.g. ANT, the hexokinase-ANT complex) by cytosolic PAR polymers [8,46,47], 4) impairs mitophagy and nuclear-mitochondrial protein balance [40,48].…”

Section: Mitochondrial Dysfunctionmentioning

confidence: 99%

“…different posttranslational modification may also modulate the activity of PARPs (for review see [7,8]). …”

mentioning

confidence: 99%

“…The PAR polymer is rapidly degraded in cells to ADPR. There are several enzymes capable of degrading PAR, such as poly(ADP-ribose) glycohydrolase (PARG) ADP-ribosyl-acceptor hydrolase 3 (ARH3), ADP-ribosyl lyase and macrodomain-containing proteins [8]. Poly(ADP-ribose) glycohydrolase (PARG) removes PAR reverting and reactivating PARP-1.…”

mentioning

confidence: 99%

“…Poly(ADP-ribose) glycohydrolase (PARG) removes PAR reverting and reactivating PARP-1. ADPR can be further fragmented to AMP by Nucleoside Diphosphate Linked to X (NUDIX) pyrophosphatases; increases in cellular AMP has pivotal role in mitochondrial deterioration inflicted by PARP activation [8].…”

mentioning

confidence: 99%

See 4 more Smart Citations

Poly(ADP-Ribose) Polymerases in Aging - Friend or Foe?

Vida¹,

Abdul‐Rahman²,

Mikó³

et al. 2016

CPPS

Self Cite

View full text Add to dashboard Cite

Section: Mitochondrial Dysfunctionmentioning

confidence: 99%

Section: Mitochondrial Dysfunctionmentioning

confidence: 99%

“…different posttranslational modification may also modulate the activity of PARPs (for review see [7,8]). …”

mentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

See 3 more Smart Citations

Poly(ADP-Ribose) Polymerases in Aging - Friend or Foe?

Vida¹,

Abdul‐Rahman²,

Mikó³

et al. 2016

CPPS

Self Cite

View full text Add to dashboard Cite

Mitochondria are devoid of poly(ADP‐ribose)polymerase‐1, but harbor its product oligo(ADP‐ribose)

Köritzer

Blenn

Bürkle

et al. 2021

J of Cellular Biochemistry

View full text Add to dashboard Cite

There are conflicting data about localization of poly(ADP-ribose)polymerase-1 and its product poly(ADP-ribose) in mitochondria. To finally clarify the discussion, we investigated with biochemical and cell biological methods the potential presence of poly(ADP-ribose) polymerase-1 in these organelles. Our data show that endogenous and overexpressed poly(ADP-ribose)polymerase 1 is only localized to the nucleus with a clear exclusion of cytosolic compartments. In addition, highly purified mitochondria devoid of nuclear contaminations do not contain poly(ADP-ribose)polymerase-1. Although no poly (ADP-ribose)polymerase-1 enzyme is detectable in mitochondria, a shorter variant of its product poly(ADP-ribose) is present, associated specifically with a small subset of mitochondrial proteins as revealed by immunoprecipitation and protein fingerprint analysis. These proteins are located at key-points of the Krebs-cycle, are chaperones involved in mitochondrial functionality and quality-control, and are RNA-binding proteins important for transcript stability, respectively. Of note, despite the fact that especially poly(ADP-ribose) polymerase-1 is its own major target for modification, we could not detect this enzyme by mass spectrometry in these organelles. These data suggests a new way of targeted nuclear-mitochondrial signaling, mediated by nuclear poly (ADP-ribosyl)ation dependent on poly(ADP-ribose)polymerase-1.

show abstract

Role of PARP activity in lung cancer‐induced cachexia: Effects on muscle oxidative stress, proteolysis, anabolic markers, and phenotype

Chacon-Cabrera

Mateu-Jiménez

Langohr

et al. 2017

Journal Cellular Physiology

View full text Add to dashboard Cite

Strategies to treat cachexia are still at its infancy. Enhanced muscle protein breakdown and ubiquitin-proteasome system are common features of cachexia associated with chronic conditions including lung cancer (LC). Poly(ADP-ribose) polymerases (PARP), which play a major role in chromatin structure regulation, also underlie maintenance of muscle metabolism and body composition. We hypothesized that protein catabolism, proteolytic markers, muscle fiber phenotype, and muscle anabolism may improve in respiratory and limb muscles of LC-cachectic Parp-1-deficient (Parp-1 ) and Parp-2 mice. In diaphragm and gastrocnemius of LC (LP07 adenocarcinoma) bearing mice (wild type, Parp-1 , and Parp-2 ), PARP activity (ADP-ribose polymers, pADPr), redox balance, muscle fiber phenotype, apoptotic nuclei, tyrosine release, protein ubiquitination, muscle-specific E3 ligases, NF-κB signaling pathway, markers of muscle anabolism (Akt, mTOR, p70S6K, and mitochondrial DNA) were evaluated along with body and muscle weights, and limb muscle force. Compared to wild type cachectic animals, in both respiratory and limb muscles of Parp-1 and Parp-2 cachectic mice: cancer induced-muscle wasting characterized by increased PARP activity, protein oxidation, tyrosine release, and ubiquitin-proteasome system (total protein ubiquitination, atrogin-1, and 20S proteasome C8 subunit) were blunted, the reduction in contractile myosin and atrophy of the fibers was attenuated, while no effects were seen in other structural features (inflammatory cells, internal or apoptotic nuclei), and markers of muscle anabolism partly improved. Activation of either PARP-1 or -2 is likely to play a role in muscle protein catabolism via oxidative stress, NF-κB signaling, and enhanced proteasomal degradation in cancer-induced cachexia. Therapeutic potential of PARP activity inhibition deserves attention.

show abstract

Poly(ADP-ribose) polymerases as modulators of mitochondrial activity

Cited by 100 publications

References 89 publications

Poly(ADP-Ribose) Polymerases in Aging - Friend or Foe?

Poly(ADP-Ribose) Polymerases in Aging - Friend or Foe?

Mitochondria are devoid of poly(ADP‐ribose)polymerase‐1, but harbor its product oligo(ADP‐ribose)

Role of PARP activity in lung cancer‐induced cachexia: Effects on muscle oxidative stress, proteolysis, anabolic markers, and phenotype

Contact Info

Product

Resources

About