Mitochondrion of protozoan parasite emerges as potent therapeutic target: Exciting drugs are on the horizon

Nilkantha Sen, Hemanta K. Majumder

Research output: Contribution to journalReview article

41 Citations (Scopus)

Abstract

Chemotherapy is the primary means of treating protozoan parasitic infections. A problem for chemotherapy is to find a novel and potential molecule in protozoa, which could be exploited as drug target. To reach this goal, mitochondrion of protozoa can be considered as the most valuable and potential organelle because of its unique structure and function compred to their natural host habitat. In fact, the respiratory systems of parasitic protozoa typically show greater diversity in electron pathways than do their host animals. These unique aspects of electron transport chain (ETC) complexes and their related enzymes represent promising targets for chemotherapy. A cytochrome independent Alternative Oxidase (AOX) in parasites is a leading drug target. Topoisomerases play Key functions in replication and organization of kDNA, which is present in a specialized region of unique mitochondria known as kinetoplast. They are considered as potential targets for anti-parasitic drugs. Moreover, a novel pathway of type II Fatty acid synthesis in mitochondria of trypanosomatids provides a new array of inhibitors that could be effective against these parasites. Recent studies on the emergence of drug resistance severely limit the arsenal of available drugs against protozoan parasites. Particularly, mutations of cytochrome b gene of ETC or changes in iron homeostasis by mitochondrial enzyme aconitase alter sensitivity of MDR1 and regulate resistance level to anti-parasitic drugs. This review summarizes recent state of our knowledge and understanding of the action of various therapeutically applied substances on mitochondria and their potential application in the future.

Original languageEnglish (US)
Pages (from-to)839-846
Number of pages8
JournalCurrent Pharmaceutical Design
Volume14
Issue number9
DOIs
StatePublished - Mar 1 2008

Fingerprint

Mitochondria
Parasites
Pharmaceutical Preparations
Electron Transport
Drug Therapy
Kinetoplast DNA
Protozoan Infections
Aconitate Hydratase
Therapeutics
Parasitic Diseases
Cytochromes b
Enzymes
Cytochromes
Drug Resistance
Organelles
Respiratory System
Ecosystem
Homeostasis
Fatty Acids
Iron

Keywords

  • Alternative oxidase
  • Apoptosis
  • Drug resistance
  • Electron transport chain
  • Fatty acid synthesis
  • Mitochondria
  • Protozoa
  • Topoisomerase

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology, Toxicology and Pharmaceutics(all)

Cite this

Mitochondrion of protozoan parasite emerges as potent therapeutic target : Exciting drugs are on the horizon. / Sen, Nilkantha; Majumder, Hemanta K.

In: Current Pharmaceutical Design, Vol. 14, No. 9, 01.03.2008, p. 839-846.

Research output: Contribution to journalReview article

@article{857a0739096e4fe6903168fc9907b664,
title = "Mitochondrion of protozoan parasite emerges as potent therapeutic target: Exciting drugs are on the horizon",
abstract = "Chemotherapy is the primary means of treating protozoan parasitic infections. A problem for chemotherapy is to find a novel and potential molecule in protozoa, which could be exploited as drug target. To reach this goal, mitochondrion of protozoa can be considered as the most valuable and potential organelle because of its unique structure and function compred to their natural host habitat. In fact, the respiratory systems of parasitic protozoa typically show greater diversity in electron pathways than do their host animals. These unique aspects of electron transport chain (ETC) complexes and their related enzymes represent promising targets for chemotherapy. A cytochrome independent Alternative Oxidase (AOX) in parasites is a leading drug target. Topoisomerases play Key functions in replication and organization of kDNA, which is present in a specialized region of unique mitochondria known as kinetoplast. They are considered as potential targets for anti-parasitic drugs. Moreover, a novel pathway of type II Fatty acid synthesis in mitochondria of trypanosomatids provides a new array of inhibitors that could be effective against these parasites. Recent studies on the emergence of drug resistance severely limit the arsenal of available drugs against protozoan parasites. Particularly, mutations of cytochrome b gene of ETC or changes in iron homeostasis by mitochondrial enzyme aconitase alter sensitivity of MDR1 and regulate resistance level to anti-parasitic drugs. This review summarizes recent state of our knowledge and understanding of the action of various therapeutically applied substances on mitochondria and their potential application in the future.",
keywords = "Alternative oxidase, Apoptosis, Drug resistance, Electron transport chain, Fatty acid synthesis, Mitochondria, Protozoa, Topoisomerase",
author = "Nilkantha Sen and Majumder, {Hemanta K.}",
year = "2008",
month = "3",
day = "1",
doi = "10.2174/138161208784041024",
language = "English (US)",
volume = "14",
pages = "839--846",
journal = "Current Pharmaceutical Design",
issn = "1381-6128",
publisher = "Bentham Science Publishers B.V.",
number = "9",

}

TY - JOUR

T1 - Mitochondrion of protozoan parasite emerges as potent therapeutic target

T2 - Exciting drugs are on the horizon

AU - Sen, Nilkantha

AU - Majumder, Hemanta K.

PY - 2008/3/1

Y1 - 2008/3/1

N2 - Chemotherapy is the primary means of treating protozoan parasitic infections. A problem for chemotherapy is to find a novel and potential molecule in protozoa, which could be exploited as drug target. To reach this goal, mitochondrion of protozoa can be considered as the most valuable and potential organelle because of its unique structure and function compred to their natural host habitat. In fact, the respiratory systems of parasitic protozoa typically show greater diversity in electron pathways than do their host animals. These unique aspects of electron transport chain (ETC) complexes and their related enzymes represent promising targets for chemotherapy. A cytochrome independent Alternative Oxidase (AOX) in parasites is a leading drug target. Topoisomerases play Key functions in replication and organization of kDNA, which is present in a specialized region of unique mitochondria known as kinetoplast. They are considered as potential targets for anti-parasitic drugs. Moreover, a novel pathway of type II Fatty acid synthesis in mitochondria of trypanosomatids provides a new array of inhibitors that could be effective against these parasites. Recent studies on the emergence of drug resistance severely limit the arsenal of available drugs against protozoan parasites. Particularly, mutations of cytochrome b gene of ETC or changes in iron homeostasis by mitochondrial enzyme aconitase alter sensitivity of MDR1 and regulate resistance level to anti-parasitic drugs. This review summarizes recent state of our knowledge and understanding of the action of various therapeutically applied substances on mitochondria and their potential application in the future.

AB - Chemotherapy is the primary means of treating protozoan parasitic infections. A problem for chemotherapy is to find a novel and potential molecule in protozoa, which could be exploited as drug target. To reach this goal, mitochondrion of protozoa can be considered as the most valuable and potential organelle because of its unique structure and function compred to their natural host habitat. In fact, the respiratory systems of parasitic protozoa typically show greater diversity in electron pathways than do their host animals. These unique aspects of electron transport chain (ETC) complexes and their related enzymes represent promising targets for chemotherapy. A cytochrome independent Alternative Oxidase (AOX) in parasites is a leading drug target. Topoisomerases play Key functions in replication and organization of kDNA, which is present in a specialized region of unique mitochondria known as kinetoplast. They are considered as potential targets for anti-parasitic drugs. Moreover, a novel pathway of type II Fatty acid synthesis in mitochondria of trypanosomatids provides a new array of inhibitors that could be effective against these parasites. Recent studies on the emergence of drug resistance severely limit the arsenal of available drugs against protozoan parasites. Particularly, mutations of cytochrome b gene of ETC or changes in iron homeostasis by mitochondrial enzyme aconitase alter sensitivity of MDR1 and regulate resistance level to anti-parasitic drugs. This review summarizes recent state of our knowledge and understanding of the action of various therapeutically applied substances on mitochondria and their potential application in the future.

KW - Alternative oxidase

KW - Apoptosis

KW - Drug resistance

KW - Electron transport chain

KW - Fatty acid synthesis

KW - Mitochondria

KW - Protozoa

KW - Topoisomerase

UR - http://www.scopus.com/inward/record.url?scp=44349131523&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=44349131523&partnerID=8YFLogxK

U2 - 10.2174/138161208784041024

DO - 10.2174/138161208784041024

M3 - Review article

C2 - 18473833

AN - SCOPUS:44349131523

VL - 14

SP - 839

EP - 846

JO - Current Pharmaceutical Design

JF - Current Pharmaceutical Design

SN - 1381-6128

IS - 9

ER -