Pallotta 2022 Abstract Bioblast

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Pallotta ML (2022) NAD(P)+/NAD(P)H Pool and the art of mitochondrial survival. Bioblast 2022: BEC Inaugural Conference.

Link: Bioblast 2022: BEC Inaugural Conference

Pallotta Maria Luigia (2022)

Event: Bioblast 2022

Shift in energy metabolism offers extent potential for intervention and thereby control of entire biochemical networks by identifying and targeting key control points both in physiological that pathological issues. Increasing evidence suggest that the pyridine nucleotide NAD+ has far wider biological functions than its classical role in energy metabolism. Hundreds of enzymes that catalyze substrate oxidation and, as such, it plays a key role in various biological processes such as aging, oxidative stress, epigenetics, immunological response and cell death, use coenzyme NAD+.

In 2007 Sinclair’ group referred to the ability of mitochondria to dictate cell survival as “mitochondrial oasis effect” which states that the energetic and NAD(P)+ content of mitochondria determines cell survival in face of genotoxic stress (i.e. DNA damage). Still not everything is cleared up NAD(P)+ biosynthesis in mitochondria. However, de novo and salvage pathways contribute to the biosynthesis of NAD+ in all organisms and both converge at the transfer of NMN or NaMN on to the adenylyl group of ATP under diphosphate release (NMN+ATP↔NAD++PPi). Given that NMN is a potent inhibitor of the NAD-dependent DNA ligase, NMNAT activity would scavenge NMN, ensuring at the same time, NAD supply to the ligase reaction. Thus, NMN was added to different eucaryotic cells bioenergetically active and mitochondria prepared starting from cell grown aerobically and NAD+ biosynthesis was tested by means of HPLC and spectroscopically. Thus, our studies showed evidence, that mitochondria can increase NAD(P)+content, probably via NMNAT and NADK and this mitochondrial NAD+ pathway should be better studied (i.e. its regulation with different inhibitor) as a basis for future biotechnological applications and biomedicine studies in treating disorders with perturbed NAD+ supply or homeostasis.

Keywords: bioenergetics, NAD+/NADH mitochondrial pool, cellular homeostasis, DNA damage, NMN


Affiliations

Dept Medicine and Health Sciences, Molise University, 86100 Campobasso, IT - pallottamarialuigia@gmail.com

References

  1. Pallotta ML (2014) NMN, an intermediate in the salvage pathway, helps to increase the intramitochondrial NAD+ concentration in yeast and influences NAD+/NADH ratio: possible function as metabolic read-out 65. Mosbacher Kolloquium - Molecular Protein Quality Control in Health, Aging and Disease, German Society for Biochemistry and Molecular Biology, Mosbach Germany 26th-29th March 2014
  2. Pallotta ML (2014) Mitochondrial NAD pool ad metastasis. Cells, proteins and bioprocessing (Nature) London (England) 17th-19th June 2014
  3. Pallotta ML (2015) The Aquarian Age in cancer therapy: biobankers, biomarkers, and much more↔getting of the root of the problem ↔NAD+ an ancient metabolite with surprising modernity ↔Mitochondrial NAD pool, tumour microenvironment and metastasis. Cell Symposia, Multifaceted Mitochondria, Chicago July 19-21, 2015
  4. Pallotta ML (2016) Monitoring NAD(P)H levels and their relevance to bioenergetics using fluorescence-based Strategies in salivary samples: a possible biomarker in the detection of cancer and precancer. EUSTM 2016; on New Horizons in Translational Medicine

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