The Fe-S cluster-containing NEET proteins mitoNEET and NAF-1 as chemotherapeutic targets in breast cancer

Proceedings of the National Academy of Sciences of the United States of America
Fang BaiRachel Nechushtai

Abstract

Identification of novel drug targets and chemotherapeutic agents is a high priority in the fight against cancer. Here, we report that MAD-28, a designed cluvenone (CLV) derivative, binds to and destabilizes two members of a unique class of mitochondrial and endoplasmic reticulum (ER) 2Fe-2S proteins, mitoNEET (mNT) and nutrient-deprivation autophagy factor-1 (NAF-1), recently implicated in cancer cell proliferation. Docking analysis of MAD-28 to mNT/NAF-1 revealed that in contrast to CLV, which formed a hydrogen bond network that stabilized the 2Fe-2S clusters of these proteins, MAD-28 broke the coordinative bond between the His ligand and the cluster's Fe of mNT/NAF-1. Analysis of MAD-28 performed with control (Michigan Cancer Foundation; MCF-10A) and malignant (M.D. Anderson-metastatic breast; MDA-MB-231 or MCF-7) human epithelial breast cells revealed that MAD-28 had a high specificity in the selective killing of cancer cells, without any apparent effects on normal breast cells. MAD-28 was found to target the mitochondria of cancer cells and displayed a surprising similarity in its effects to the effects of mNT/NAF-1 shRNA suppression in cancer cells, causing a decrease in respiration and mitochondrial membrane potential, as...Continue Reading

References

Aug 28, 1998·Science·D R Green, J C Reed
Jan 26, 2007·Organic & Biomolecular Chemistry·Ayse BatovaEmmanuel A Theodorakis
May 15, 2007·Molecular Aspects of Medicine·Jiri NeuzilStephen J Ralph
Sep 4, 2007·Proceedings of the National Academy of Sciences of the United States of America·Mark L PaddockPatricia A Jennings
Jul 8, 2009·Journal of Molecular Biology·Andrea R ConlanMark L Paddock
Nov 13, 2009·Organic & Biomolecular Chemistry·Oraphin ChantarasriwongEmmanuel A Theodorakis
May 15, 2010·Nature Reviews. Drug Discovery·Simone FuldaGuido Kroemer
Jul 6, 2010·Mitochondrion·Lucia BiasuttoJiri Neuzil
Jul 22, 2010·Chemistry : a European Journal·Oraphin ChantarasriwongEmmanuel A Theodorakis
Nov 26, 2010·British Journal of Pharmacology·Yang-Sung SohnZ Ioav Cabantchik
Jul 27, 2011·Proceedings of the National Academy of Sciences of the United States of America·John A ZurisRachel Nechushtai
Aug 3, 2011·Proceedings of the National Academy of Sciences of the United States of America·Dima KozakovSandor Vajda
Feb 22, 2012·Human Molecular Genetics·Natasha C ChangGordon C Shore
Apr 26, 2012·Chembiochem : a European Journal of Chemical Biology·Gianni GuizzuntiEmmanuel A Theodorakis
Apr 9, 2013·Organic & Biomolecular Chemistry·Kristyna M ElbelEmmanuel A Theodorakis
Aug 21, 2013·Proceedings of the National Academy of Sciences of the United States of America·Yang-Sung SohnRon Mittler
Apr 8, 2014·Proceedings of the National Academy of Sciences of the United States of America·Sagi TamirRachel Nechushtai
Jun 11, 2014·Acta Crystallographica. Section D, Biological Crystallography·Sagi TamirRachel Nechushtai

❮ Previous
Next ❯

Citations

Jul 29, 2016·Proceedings of the National Academy of Sciences of the United States of America·Kendrick H YimLeonard Neckers
Sep 14, 2016·Proceedings of the National Academy of Sciences of the United States of America·Merav Darash-YahanaRachel Nechushtai
Aug 12, 2016·Biochemical and Biophysical Research Communications·Hua YuanDaolin Tang
Feb 16, 2018·Oxidative Medicine and Cellular Longevity·Laurence VernisMeng-Er Huang
Dec 2, 2015·Journal of Cell Science·Sarah H HoltRon Mittler
Nov 2, 2016·Antimicrobial Agents and Chemotherapy·Hangjun KeAkhil B Vaidya
Dec 21, 2017·Proceedings of the National Academy of Sciences of the United States of America·Colin H LipperPatricia A Jennings
Apr 24, 2019·The Journal of Pharmacology and Experimental Therapeutics·Werner J GeldenhuysLaura F Gibson
Sep 19, 2019·Proceedings of the National Academy of Sciences of the United States of America·Colin H LipperPatricia A Jennings
Jan 14, 2017·The Journal of Biological Chemistry·Zishuo ChengHuangen Ding
Mar 21, 2018·Scientific Reports·Soham SenguptaRon Mittler
Dec 3, 2016·Proceedings of the National Academy of Sciences of the United States of America·Fang BaiJosé N Onuchic
Jul 19, 2017·Proceedings of the National Academy of Sciences of the United States of America·Alexandre VernayPierre Cosson
Jun 18, 2017·Scientific Reports·Xian-Li JiangFaruck Morcos
Sep 12, 2018·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Kai Cai, John L Markley
Feb 13, 2018·Journal of Biological Inorganic Chemistry : JBIC : a Publication of the Society of Biological Inorganic Chemistry·Ola KarmiRachel Nechushtai
Apr 21, 2017·PloS One·Ola KarmiRon Mittler
Oct 12, 2017·Metallomics : Integrated Biometal Science·C WachnowskyJ A Cowan
Feb 23, 2018·Journal of Biological Inorganic Chemistry : JBIC : a Publication of the Society of Biological Inorganic Chemistry·Wilfred R Hagen
Feb 22, 2018·Antioxidants & Redox Signaling·Ron MittlerRachel Nechushtai
Feb 19, 2019·Chemical Science·Anat Iosub-AmirRachel Nechushtai
Aug 4, 2020·Biochimica Et Biophysica Acta. Molecular Cell Research·Rachel NechushtaiRon Mittler

❮ Previous
Next ❯

Related Concepts

Related Feeds

Autophagy & Metabolism

Autophagy preserves the health of cells and tissues by replacing outdated and damaged cellular components with fresh ones. In starvation, it provides an internal source of nutrients for energy generation and, thus, survival. A powerful promoter of metabolic homeostasis at both the cellular and whole-animal level, autophagy prevents degenerative diseases. It does have a downside, however--cancer cells exploit it to survive in nutrient-poor tumors.

Cancer Metabolic Reprogramming (Keystone)

Cancer metabolic reprogramming is important for the rapid growth and proliferation of cancer cells. Cancer cells have the ability to change their metabolic demands depending on their environment, regulated by the activation of oncogenes or loss of tumor suppressor genes. Here is the latest research on cancer metabolic reprogramming.

Autophagy & Model Organisms

Autophagy is a cellular process that allows degradation by the lysosome of cytoplasmic components such as proteins or organelles. Here is the latest research on autophagy & model organisms

Cancer Metabolic Reprogramming

Cancer metabolic reprogramming is important for the rapid growth and proliferation of cancer cells. Cancer cells have the ability to change their metabolic demands depending on their environment, regulated by the activation of oncogenes or loss of tumor suppressor genes. Here is the latest research on cancer metabolic reprogramming.

Autophagy & Disease

Autophagy is an important cellular process for normal physiology and both elevated and decreased levels of autophagy are associated with disease. Here is the latest research.

Cancer Metabolism: Therapeutic Targets

Targeting the mechanisms by which cancer cells acquire energy for metabolic needs is a therapeutic target. Discover the latest research on cancer metabolism and therapeutic targets.

Parkinson's Disease & Autophagy (MDS)

Autophagy leads to degradation of damaged proteins and organelles by the lysosome. Impaired autophagy has been implicated in several diseases. Here is the role of autophagy in Parkinson’s disease.