Blood-Feeding Induces Reversible Functional Changes in Flight Muscle Mitochondria of Aedes aegypti Mosquito

Background Hematophagy poses a challenge to blood-feeding organisms since products of blood digestion can exert cellular deleterious effects. Mitochondria perform multiple roles in cell biology acting as the site of aerobic energy-transducing pathways, and also an important source of reactive oxygen species (ROS), modulating redox metabolism. Therefore, regulation of mitochondrial function should be relevant for hematophagous arthropods. Here, we investigated the effects of blood-feeding on flight muscle (FM) mitochondria from the mosquito Aedes aegypti, a vector of dengue and yellow fever. Methodology/Principal Findings Blood-feeding caused a reversible reduction in mitochondrial oxygen consumption, an event that was parallel to blood digestion. These changes were most intense at 24 h after blood meal (ABM), the peak of blood digestion, when oxygen consumption was inhibited by 68%. Cytochromes c and a+a 3 levels and cytochrome c oxidase activity of the electron transport chain were all reduced at 24 h ABM. Ultrastructural and molecular analyses of FM revealed that mitochondria fuse upon blood meal, a condition related to reduced ROS generation. Consistently, BF induced a reversible decrease in mitochondrial H2O2 formation during blood digestion, reaching their lowest values at 24 h ABM where a reduction of 51% was observed. Conclusion Blood-feeding triggers functional and structural changes in hematophagous insect mitochondria, which may represent an important adaptation to blood feeding.

[1]  Jean-Claude Martinou,et al.  SLP‐2 is required for stress‐induced mitochondrial hyperfusion , 2009, The EMBO journal.

[2]  K. White,et al.  Long-lived Indy induces reduced mitochondrial reactive oxygen species production and oxidative damage , 2009, Proceedings of the National Academy of Sciences.

[3]  D. Wallace,et al.  Heterozygous Mutation of Opa1 in Drosophila Shortens Lifespan Mediated through Increased Reactive Oxygen Species Production , 2009, PloS one.

[4]  C. Giulivi,et al.  Metabolic pathways in Anopheles stephensi mitochondria. , 2008, The Biochemical journal.

[5]  Y. Yoon,et al.  Mitochondrial fission mediates high glucose-induced cell death through elevated production of reactive oxygen species. , 2008, Cardiovascular research.

[6]  Min Wu,et al.  Fission and selective fusion govern mitochondrial segregation and elimination by autophagy , 2008, The EMBO journal.

[7]  Guoli Zhou,et al.  Fate of blood meal iron in mosquitoes. , 2007, Journal of insect physiology.

[8]  D. Chan,et al.  Functions and dysfunctions of mitochondrial dynamics , 2007, Nature Reviews Molecular Cell Biology.

[9]  Anja Voigt,et al.  Glucose restriction extends Caenorhabditis elegans life span by inducing mitochondrial respiration and increasing oxidative stress. , 2007, Cell metabolism.

[10]  C. Hoppel,et al.  Structure of cristae in cardiac mitochondria of aged rat , 2006, Mechanisms of Ageing and Development.

[11]  M. Freeman,et al.  Normal Mitochondrial Dynamics Requires Rhomboid-7 and Affects Drosophila Lifespan and Neuronal Function , 2006, Current Biology.

[12]  M. Sorgine,et al.  Insect Biochemistry and Molecular Biology Minireview Adaptations against Heme Toxicity in Blood-feeding Arthropods , 2022 .

[13]  J. Pennington,et al.  Reevaluation of the role of early trypsin activity in the transcriptional activation of the late trypsin gene in the mosquito Aedes aegypti. , 2006, Insect biochemistry and molecular biology.

[14]  Y. Yoon,et al.  Increased production of reactive oxygen species in hyperglycemic conditions requires dynamic change of mitochondrial morphology. , 2006, Proceedings of the National Academy of Sciences of the United States of America.

[15]  A. Peixoto,et al.  Isolation of a fragment homologous to the rp49 constitutive gene of Drosophila in the Neotropical malaria vector Anopheles aquasalis (Diptera: Culicidae). , 2005, Memorias do Instituto Oswaldo Cruz.

[16]  M. Brand,et al.  The topology of superoxide production by complex III and glycerol 3-phosphate dehydrogenase in Drosophila mitochondria. , 2005, Biochimica et biophysica acta.

[17]  R. S. Sohal,et al.  Age-associated decline in mitochondrial respiration and electron transport in Drosophila melanogaster. , 2005, The Biochemical journal.

[18]  A. James,et al.  Microarray analysis of genes showing variable expression following a blood meal in Anopheles gambiae , 2005, Insect molecular biology.

[19]  L. Partridge,et al.  Calories Do Not Explain Extension of Life Span by Dietary Restriction in Drosophila , 2005, PLoS biology.

[20]  T. Bradley,et al.  Insects breathe discontinuously to avoid oxygen toxicity , 2005, Nature.

[21]  Guoli Zhou,et al.  Utilization of pre-existing energy stores of female Aedes aegypti mosquitoes during the first gonotrophic cycle. , 2004, Insect biochemistry and molecular biology.

[22]  L. S. Ross,et al.  Blood meal induces global changes in midgut gene expression in the disease vector, Aedes aegypti. , 2003, Insect biochemistry and molecular biology.

[23]  L. Partridge,et al.  Superoxide and hydrogen peroxide production by Drosophila mitochondria. , 2003, Free radical biology & medicine.

[24]  J. Ribeiro.  A catalogue of Anopheles gambiae transcripts significantly more or less expressed following a blood meal. , 2003, Insect biochemistry and molecular biology.

[25]  J. Pennington,et al.  Erratum to “The role of hemolymph proline as a nitrogen sink during blood meal digestion by the Mosquito Aedes aegypti” [Journal of Insect Physiology 49 (2) pp. 115-121 (2003)] , 2003 .

[26]  M. Wells,et al.  Proline can be utilized as an energy substrate during flight of Aedes aegypti females. , 2003, Journal of insect physiology.

[27]  J. Pennington,et al.  The role of hemolymph proline as a nitrogen sink during blood meal digestion by the mosquito Aedes aegypti. , 2003, Journal of insect physiology.

[28]  P. Brookes,et al.  Mitochondria: regulators of signal transduction by reactive oxygen and nitrogen species. , 2002, Free radical biology & medicine.

[29]  P. Oliveira,et al.  Vampires, Pasteur and reactive oxygen species , 2002, FEBS letters.

[30]  M. Jacobs-Lorena,et al.  Aedes aegypti peritrophic matrix and its interaction with heme during blood digestion. , 2002, Insect Biochemistry and Molecular Biology.

[31]  M. L. Genova,et al.  Role of Mitochondria in Oxidative Stress and Aging , 2002, Annals of the New York Academy of Sciences.

[32]  M. Pfaffl,et al.  A new mathematical model for relative quantification in real-time RT-PCR. , 2001, Nucleic acids research.

[33]  C. Kahn,et al.  Frataxin activates mitochondrial energy conversion and oxidative phosphorylation. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[34]  P. Defossez,et al.  Requirement of NAD and SIR2 for life-span extension by calorie restriction in Saccharomyces cerevisiae. , 2000, Science.

[35]  Y. Kaneda,et al.  Normalizing mitochondrial superoxide production blocks three pathways of hyperglycaemic damage , 2000, Nature.

[36]  M. Wells,et al.  A molecular view of trypsin synthesis in the midgut of Aedes aegypti. , 1999, Journal of insect physiology.

[37]  D. Radisky,et al.  The Yeast Frataxin Homologue Mediates Mitochondrial Iron Efflux , 1999, The Journal of Biological Chemistry.

[38]  R. S. Sohal,et al.  Mitochondrial adenine nucleotide translocase is modified oxidatively during aging. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[39]  R. S. Sohal,et al.  Oxidative damage during aging targets mitochondrial aconitase. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[40]  V. Skulachev,et al.  High protonic potential actuates a mechanism of production of reactive oxygen species in mitochondria , 1997, FEBS letters.

[41]  K. G. Hales,et al.  Developmentally Regulated Mitochondrial Fusion Mediated by a Conserved, Novel, Predicted GTPase , 1997, Cell.

[42]  R. Weindruch,et al.  Oxidative Stress, Caloric Restriction, and Aging , 1996, Science.

[43]  P. Oliveira,et al.  Antioxidant Role of Rhodnius prolixus Heme-binding Protein , 1995, The Journal of Biological Chemistry.

[44]  S. Moncada,et al.  Reversible inhibition of cytochrome c oxidase, the terminal enzyme of the mitochondrial respiratory chain, by nitric oxide , 1994, FEBS letters.

[45]  E. Bursell.  Substrates of oxidative metabolism in dipteran flight muscle. , 1975, Comparative biochemistry and physiology. B, Comparative biochemistry.

[46]  H. Briegel,et al.  Relationship between protein and proteolytic activity in the midgut of mosquitoes. , 1975, Journal of insect physiology.

[47]  B Chance,et al.  The mitochondrial generation of hydrogen peroxide. General properties and effect of hyperbaric oxygen. , 1973, The Biochemical journal.

[48]  B. Tandler,et al.  RIBOFLAVIN AND MOUSE HEPATIC CELL STRUCTURE AND FUNCTION , 1969, The Journal of cell biology.

[49]  Y. Avi-Dor,et al.  Studies on the adenosine triphosphate-phosphate exchange and the hydrolysis of adenosine triphosphate catalysed by a particulate fraction from the mosquito. , 1959, Biochemical Journal.

[50]  Y. Avi-Dor,et al.  The oxidative activity of particulate fractions from mosquitoes. , 1957, The Biochemical journal.

[51]  B CHANCE,et al.  Respiratory enzymes in oxidative phosphorylation. II. Difference spectra. , 1955, The Journal of biological chemistry.

[52]  B CHANCE,et al.  Respiratory enzymes in oxidative phosphorylation. III. The steady state. , 1955, The Journal of biological chemistry.

[53]  Oliver H. Lowry,et al.  Protein measurement with the Folin phenol reagent. , 1951, The Journal of biological chemistry.

[54]  A. Clements.  Development, nutrition, and reproduction , 2008 .

[55]  L. Partridge,et al.  The effect of dietary restriction on mitochondrial protein density and flight muscle mitochondrial morphology in Drosophila. , 2006, The journals of gerontology. Series A, Biological sciences and medical sciences.

[56]  V. Wigglesworth,et al.  The supply of oxygen to the flight muscles of insects: a theory of tracheole physiology. , 1982, Tissue & cell.

[57]  M. Rockstein.  The physiology of Insecta , 1964 .