ABB  Vol.1 No.2 , June 2010
Mitochondria: transportation, distribution and function during spermiogenesis
Author(s) Xiao Sun, Wan-Xi Yang
Spermiogenesis is a dynamic process which includes organelle reorganization and new structure formation. The morphology and distribution of the mitochondria in germ cells change to accommodate the cellular requirement. Multiple molecular motors and related proteins participate in carrying and anchoring mitochondria to the midpiece during spermiogenesis and this process is regulated precisely. Energetic metabolism provides energy for cellular activity and influences sperm survival and motility directly. Ubiquitination of mitochondria takes place during spermiogenesis, which has been implicated in sperm quality control and mitochondrial inheritance. In light of the essential roles of mitochondria in energy production, calcium homeostasis and apoptosis, mitochondria dysfunction cause severe human diseases, such as male infertility. The present study paves a way for a more detailed exploration of the biology of mitochondria during spermiogenesis.

Cite this paper
nullSun, X. and Yang, W. (2010) Mitochondria: transportation, distribution and function during spermiogenesis. Advances in Bioscience and Biotechnology, 1, 97-109. doi: 10.4236/abb.2010.12014.
[1]   Abou-Haila, A. and Tulsiani, D.R. (2000) Mammalian sperm acrosome: Formation, contents, and function. Archives of Biochemistry and Biophysics, 379(2), 173-182.

[2]   Fawcett, D.W. (1975) The mammalian spermatozoon. Developmental Biology, 44(2), 394-436.

[3]   Kamp, G., Büsselmann, G. and Lauterwein, J. (1996) Spermatozoa: Models for studying regulatory aspects of energy metabolism. Experientia, 52(2), 487-493.

[4]   Ruiz-Pesini, E., Diez, C., Lapeña, A.C., Pérez-Martos, A., Montoya, J., Alvarez, E., Arenas, J. and López-Pérez, M.J. (1998) Correlation of sperm motility with mitochondrial enzymatic activities. Clinical Chemistry, 44(8), 1616-1620.

[5]   Krisfalusi, M., Miki, K., Magyar, P.L. and O'Brien, D.A. (2006) Multiple glycolytic enzymes are tightly bound to the fibrous sheath of mouse spermatozoa. Biology of Reproduction, 75(2), 270-278.

[6]   Molloy, P.P., Goodwin, N.B., Côté, I.M., Reynolds, J.D., Gage, M.J. Mukai, C. and Okuno, M. (2004) Glycolysis plays a major role for adenosine triphosphate supplementation in mouse sperm flagellar movement. Biology of Reproduction, 71(2), 540-547.

[7]   Ford, W.C.L. (2006) Glycolysis and sperm motility: Does a spoonful of sugar help the flagellum go round? Human Reproduction Update, 12(3), 269-274.

[8]   Waterman-Storer, C.M., Karki, S.B., Kuznetsov, S.A., Tabb, J.S., Weiss, D.G., Langford, G.M. and Holzbaur, E.L. (1997) The interaction between cytoplasmic dynein and dynactin is required for fast axonal transport. Proceedings of the National Academy of Sciences, 94(22), 12180-12185

[9]   Tanaka, Y., Kanai, Y., Okada, Y., Nonaka, S., Takeda, S., Harada, A. and Hirokawa, N. (1998) Targeted disruption of mouse conventional kinesin heavy chain, kif5b, results in abnormal perinuclear clustering of mitochondria. Cell, 93(7), 1147-1158.

[10]   Nangaku, M., Sato-Yoshitake, R., Okada, Y., Noda, Y., Takemura, R., Yamazaki, H. and Hirokawa, N. (1994) KIF1B, a novel microtubule plus end-directed monomeric motor protein for transport of mitochondria. Cell, 79(7), 1209-1220.

[11]   Hirokawa, N. and Takemura, R. (2005) Molecular motors and mechanisms of directional transport in neurons. Nature Reviews Neuroscience, 6(3), 201-214.

[12]   Boldogh, I.R. and Pon, L.A. (2007) Mitochondria on the move. TRENDS in Cell Biology, 17(10), 502-510.

[13]   Altmann, K., Frank, M., Neumann, D., Jakobs, S. and Westermann, B. (2008) The class V myosin motor protein, myo2, plays a major role in mitochondrial motility in Saccharomyces cerevisiae. The Journal of Cell Biology, 181(1), 119-130.

[14]   Quintero, O.A., Divito, M.M., Adikes, R.C., Kortan, M.B., Case, L.B., Lier, A.J., Panaretos, N.S., Slater, S.Q., Rengarajan, M., Feliu, M., and Cheney, R.E. (2009) Human Myo19 is a novel myosin that associates with mitochondria. Current Biology, 19(23), 2008-2013.

[15]   Sutovsky, P. (2003) Ubiquitin-dependent proteolysis in mammalian spermatogenesis, fertilization, and sperm quality control: Killing three birds with one stone. Microscopy Research and Technique, 61(1), 88-102.

[16]   Clermont, Y. and Leblond, C.P. (1955) Spermiogenesis of man, monkey, ram and other mammals as shown by the “periodic acid-schiff technique”. American Journal of Anatomy, 96(2), 229-253.

[17]   Bedford, J.M. and Nicander, L. (1971) Ultrastructural changes in the acrosome and sperm membranes during maturation of spermatozoa in the testis and epididymis of the rabbit and monkey. Journal of Anatomy, 108(3), 527-543.

[18]   Clermont, Y., Oko, R. and Hermo, L. (1991) Cell biology of mammalian spermiogenesis. In: Desjardins, C. and Ewing, L.L., Ed., Cell and Molecular Biology of the Testis, Oxford University Press, New York, 332-376.

[19]   Breed, W.G. (2004) The spermatozoon of Eurasian murine rodents: Its morphological diversity and evolution. Journal of morphology, 261(1), 52-69.

[20]   Afzelius, B. (1959) Electron microscopy of the sperm tail; results obtained with a new fixative. Journal of Biophysical and Biochemical Cytology, 5(2), 269-278.

[21]   Eddy, E.M., Toshimori, K. andO'Brien, D.A. (2003) Fibrous sheath of mammalian spermatozoa. Microscopy Research and Technique, 61(1), 103-115.

[22]   Breucker, H., Schäfer, E. and Holstein, A.F. (1985) Morphogenesis and fate of the residual body in human spermiogenesis. Cell and Tissue Research, 240(2), 303-309.

[23]   Fawcett, D.W. (1970) A comparative view of sperm ultrastructure. Biology of Reproduction Supplement, 2(2), 90-127.

[24]   De Martino, C., Floridi, A., Marcante, M.L., Malorni, W., Barcellona, P.S., Bellocci, M. and Silvestrini, B. (1979) Morphological, histochemical and biochemical studies on germ cell mitochondria of normal rats. Cell and Tissue Research, 196(1), 1-22.

[25]   Ho, H.C. and Wey, S. (2007) Three dimensional rendering of the mitochondrial sheath morphogenesis during mouse spermiogenesis. Microscopy Research and Technique, 70(8), 719-723.

[26]   Buckland-Nicks, J. and Scheltema, A. (1995) Was internal fertilization an innovation of early bilateral evidence from sperm structure of a mollusc. Proceedings of Biological Sciences, 261(1360), 11-18.

[27]   Healy, J.M., Keys, J.L. and Daddow, L.Y.M. (2000) Comparative sperm ultrastructure in pteriomorphia bivalves with special reference to phylogenetic and taxonomic implications. In Harper, E., Taylor, J.D. and Crame, J.A., Ed., Evolutionary Biology of the Bivalvia, Geological Society, London, Special Publications, 177, 169-190.

[28]   Gwo, J.C., Yang, W.T., Sheu, Y.T. and Cheng, H.Y. (2002) Spermatozoan morphology of four species of bivalve (Heterodonta, Veneridae) from Taiwan. Tissue and Cell, 34(1), 39-43.

[29]   Gwo, J.C., Chiu, J.Y., Lin, C.Y., Su, Y. and Yu, S.L. (2005) Spermatozoan ultrastructure of four Sparidae fishes: Acanthopagrus berda, Acanthopagrus australis, Lagodon rhomboids and Archosargus probatocephus. Tissue and Cell, 37(2), 109-115.

[30]   Zhu, J.Q., Dahms, H.U. and Yang, W.X. (2008) Ultrastructure of the mature spermatozoon of the bivalve Scapharca broughtoni. (Mollusca: Bivalvia: Arcidae). Micron, 39(8), 1205-1209.

[31]   Zhu, J.Q. and Yang, W.X. (2009) Ultrastructure of the mature spermatozoon of the bivalve Estellarca olivacea (Mollusca: Bivalvia: Arcidae) and its phylogenetic implications. Acta Biologica Hungarica, 60(1), 27-34.

[32]   Maxwell, W.L. (1975) Spermiogenesis of Eusepia officinalis (L.), Loligo forbesi (Steenstrup) and Alloteuthits subuclata (L.) (Cephalopoda, Decapoda). Proceedings of Biological Sciences, 191(1105), 527-535.

[33]   Selmi, M.G. (1996) Spermatozoa of two Eledone species (Cephalopoda, Octopoda). Tissue and Cell, 28(5), 613- 620.

[34]   Zhu, J.Q., Yang, W.X., You, Z.J. and Jiao, H.F. (2005) The ultrastructure of the spermatozoon of Octopus tankahkeei. Journal of Shellfish Research, 24(4), 1203- 1207.

[35]   Roura, A., Guerra, A., González, A.F. and Pascual, S. (2010) Sperm ultrastructure in Bathypolypus bairdii and B. sponsalis (Cephalopoda, Octopoda). Journal of Morphology, 271(2), 143-151.

[36]   Quagio-Grassiotto, I., Antoneli, F.N. and Oliveira, C. (2003) Spermiogenesis and sperm ultrastructure in Cichla intermedia with some considerations about Labroidei spermatozoa (Teleostei, Perciformes, Cichlidae). Tissue and Cell, 35(6), 441-446.

[37]   Gusmão-Pompiani, P., Oliveira, C. and Quagio-Grass- iotto, I. (2005) Spermatozoa ultrastructure in Sciaenidae and Polynemidae (Teleostei: Perciformes) with some consideration on Percoidei spermatozoa ultrastructure. Tissue and Cell, 37(3), 177-191.

[38]   Gage, M.J. (1998) Mammalian sperm morphometry. Proceedings of Biological Sciences/The Royal Society, 265(1391), 97-103.

[39]   Gomendio, M. and Roldan, E.R. (2008) Implications of diversity in sperm size and function for sperm competition and fertility. International Journal of Developmental Biology, 52(5-6), 439-447.

[40]   Ball, M.A. and Parker, G.A. (1996) Sperm competition games: External fertilization and “adapative” infertility. Journal of Theoretical Biology, 180(2), 141-150.

[41]   Hirokawa, N., Noda, Y. and Okada, Y. (1998) Kinesin and dynein superfamily proteins in organelle transport and cell division. Current Opinion in Cell Biology, 10(1), 60-73.

[42]   Hirokawa, N. (1998) Kinesin and dynein superfamily proteins and the mechanism of organelle transport. Science, 279(5350), 519-526.

[43]   Wozniak, M.J., Melzer, M., Dorner, C., Haring, H.U. and Lammers, R. (2005) The novel protein KBP regulates mitochondria localization by interaction with a kinesin- like protein. BMC Cell Biology, 6(1), 1-15.

[44]   Khodjakov, A., Lizunova, E.M., Minin, A.A., Koonce, M.P. and Gyoeva, F.K. (1998) A specific light chain of kinesin associates with mitochondria in cultured cells. Molecular Biology of the Cell, 9(2), 333-343.

[45]   Cai, Q., Gerwin, C. and Sheng, Z.H. (2005) Syntabulin- mediated anterograde transport of mitochondria along neuronal processes. The Journal of Cell Biology, 170(6), 959-969.

[46]   Horiuchi, D., Barkus, R.V., Pilling, A.D., Gassman, A. and Saxton, W.M. (2005) APLIP1, a kinesin binding JIP-1/JNK scaffold protein, influences the axonal transport of both vesicles and mitochondria in Drosophila. Current Biology, 15(23), 2137-2141.

[47]   Glater, E.E., Megeath, L.J., Stowers, R.S. and Schwarz, T.L. (2006) Axonal transport of mitochondria requires milton to recruit kinesin heavy chain and is light chain independent. The Journal of Cell Biology, 173(4), 545- 557.

[48]   MacAskill, A.F., Brickley, K., Stephenson, F.A. and Kittler, J.T. (2009) GTPase dependent recruitment of Grif-1 by Miro1 regulates mitochondrial trafficking in hippocampal neurons. Molecular and Cellular Neuroscience, 40(3), 301-312.

[49]   Frederick, R.L., McCaffery, J.M., Cunningham, K.W., Okamoto, K. and Shaw, J.M. (2004) Yeast Miro GTPase, Gem1p, regulates mitochondrial morphology via a novel pathway. The Journal of Cell Biology, 167(1), 87-98.

[50]   MacAskill, A.F., Rinholm, J.E., Twelvetrees, A.E., Arancibia-Carcamo, I.L., Muir, J., Fransson, A., Aspenstrom, P., Attwell, D. and Kittler, J.T. (2009) Miro1 is a calcium sensor for glutamate receptor-dependent localization of mitochondria at synapses. Neuron, 61(4), 541-55.

[51]   Russo, G.J., Louie, K., Wellington, A., Macleod, G.T., Hu, F., Panchumarthi, S. and Zinsmaier, K.E. (2009) Drosophila Miro is required for both anterograde and retrograde axonal mitochondrial transport. Journal of Neuroscience, 29(17), 5443-5455.

[52]   Horiuchi, D., Collins, C.A., Bhat, P, Barkus, R.V., Diantonio, A. and Saxton, W.M. (2007) Control of a kinesin- cargo linkage mechanism by JNK pathway kinases. Current Biology, 17(15), 1313-1317.

[53]   Varadi, A., Johnson-Cadwell, L.I., Cirulli, V., Yoon, Y., Allan, V.J. and Rutter, G.A. (2004) Cytoplasmic dynein regulates the subcellular distribution of mitochondria by controlling the recruitment of the fission factor dynamin- related protein-1. Journal of Cell Science, 117(19), 4389-4400.

[54]   Haghnia, M., Cavalli, V., Shah, S.B., Schimmelpfeng, K., Brusch, R., Yang, G., Herrera, C., Pilling, A. and Goldstein, L.S. (2007) Dynactin is required for coordinated bidirectional motility, but not for dynein membrane attachment. Molecular Biology of the Cell, 18(6), 2081- 2089.

[55]   Pilling, A.D., Horiuchi, D., Lively, C.M. and Saxton, W.M. (2006) Kinesin-1 and dynein are the primary motors for fast transport of mitochondria in drosophila motor axons. Molecular Biology of the Cell, 17(4), 2057- 2068.

[56]   Ligon, L.A., Tokito, M., Finklestein, J.M., Grossman, F.E. and Holzbaur, E.L. (2004) A direct interaction between cytoplasmic dynein and kinesin I may coordinate motor activity. Journal of Biological Chemistry, 279(18), 19201- 19208.

[57]   De Vos, K., Severin, F., Van Herreweghe, F., Vancompernolle, K., Goossens, V., Hyman, A. and Grooten, J. (2000) Tumor necrosis factor induces hyperphosphorylation of kinesin light chain and inhibits kinesin-mediated transport of mitochondria. The Journal of Cell Biology, 149(6), 1207-1214.

[58]   Reynolds, I.J. and Rintoul, G.L. (2004) Mitochondrial stop and go: Signals that regulate organelle movement. Science's STKE, 2004(251), 46.

[59]   Chada, S.R. and Hollenbeck, P.J. (2003) Mitochondrial movement and positioning in axons: The role of growth factor signaling. The Journal of Experimental Biology, 206(12), 1985-1992.

[60]   Itoh, T., Watabe, A., Toh-E, A. and Matsui, Y. (2002) Complex formation with Ypt11p, a rab-Type small GTPase, is essential to facilitate the function of myo2p, a class V Myosin, in mitochondrial Ddistribution in Saccharomyces cerevisiae. Molecular and Cellular Biology, 22(22), 7744-7757.

[61]   Kierszenbaum, A.L. (2002). Intramanchette transport (IMT): Managing the making of the spermatid head, centrosome, and tail. Molecular Reproduction and Development, 63(1), 1-4.

[62]   Yoshida, T., Ioshii, S.O., Imanaka-Yoshida, K. and Izutsu, K. (1994) Association of cytoplasmic dynein with manchette microtubules and spermatid nuclear envelope during spermiogenesis in rats. Journal of Cell Science, 107(3), 625-633.

[63]   Cole, D.G., Diener, D.R., Himelblau, A.L., Beech, P.L., Fuster, J.C. and Rosenbaum, J.L. (1998) Chlamydomonas kinesin-II-dependent intraflagellar transport (IFT): IFT particles contain proteins required for ciliary assembly in Caenorhabditis elegans sensory neurons. The Journal of Cell Biology, 141(4), 993-1008.

[64]   Miller, M.G., Mulholland, D.J. and Vogl, A.W. (1999) Rat testis motor proteins associated with spermatid translocation (dynein) and spermatid flagella (kinesin-II). Biology of Reproduction, 60(4), 1047-1056.

[65]   Kierszenbaum, A.L., Rivkin, .E and Tres, L.L. (2003) The actin-based motor myosin Va is a component of the acroplaxome, an acrosome-nuclear envelope junctional plate, and of manchette-associated vesicles. Cytogenetic and Genome Research, 103(3-4), 337-344.

[66]   Hayasaka, S., Terada, Y., Suzuki, K., Murakawa, H., Tachibana, I., Sankai, T., Murakami, T., Yaegashi, N. and Okamura, K. (2008) Intramanchette transport during primate spermiogenesis: expression of dynein, myosin Va, motor recruiter myosin Va, VIIa-Rab27a/b interacting protein, and Rab27b in the manchette during human and monkey spermiogenesis. Asian Journal of Andrology, 10(4), 561-568.

[67]   Ou, G., Blacque, O.E., Snow, J.J., Leroux, M.R. and Scholey, J.M. (2005) Functional coordination of intraflagellar transport motors. Nature, 436(7050), 583-587.

[68]   Hancock, W.O. (2008) Intracellular transport: Kinesins working together. Current Biology, 18(16), R715-17.

[69]   Bouchard, M.J., Dong, Y., McDermott, B.M. Jr., Lam, D.H., Brown, K.R., Shelanski, M., Bellvé, A.R. and Racaniello, V.R. (2000) Defects in nuclear and cytoskeletal morphology and mitochondrial localization in spermatozoa of mice lacking nectin-2, a component of cell-cell adherens junctions. Molecular and Cellular Biology, 20(8), 2865-2873.

[70]   Doiguchi, M., Mori, T., Toshimori, K., Shibata, Y. and Iida, H. (2002) Spergen-1 might be an adhesive molecule associated with mitochondria in the middle piece of spermatozoa. Developmental Biology, 252(1), 127-137.

[71]   Doiguchi, M., Yamashita, H., Ichinose, J., Mori, T., Shibata, Y. and Iida, H. (2002) Complementary DNA cloning and characterization of rat spergen-1, a spermatogenic cell-specific gene-1, containing mitochondria- targeting signal. Biology of Reproduction, 66(5), 1462- 1470.

[72]   Junco, A., Bhullar, B., Tarnasky, H.A. and van der Hoorn, F.A. (2001) Kinesin light-chain KLC3 expression in testis is restricted to spermatids. Biology of Reproduction, 64(5), 1320-1330.

[73]   Zhang, Y., Oko, R. and van der Hoorn, F.A. (2004) Rat kinesin light chain 3 associates with spermatid mitochondria. Developmental Biology, 275(1), 23-33.

[74]   Yao, R., Ito, C., Natsume, Y., Sugitani, Y., Yamanaka, H., Kuretake, S., Yanagida, K., Sato, A., Toshimori, K. and Noda, T. (2002) Lack of acrosome formation in mice lacking a Golgi protein, GOPC, 99(17), 11211–11216.

[75]   Escalier, D. (2006) Knockout mouse models of sperm flagellum anomalies. Human Reproduction Update, 12(4), 449-461.

[76]   Xiao, N., Kam, C., Shen, C., Jin, W., Wang, J., Lee, K.M., Jiang, L. and Xia, J. (2009) PICK1 deficiency causes male infertility in mice by disrupting acrosome formation. Journal of Clinical Investigation, 119(4), 802-812.

[77]   Wang, W.L., Yeh, S.F., Chang, Y.I., Hsiao, S.F., Lian, W.N., Lin, C.H., Huang, C.Y. and Lin, W.J. (2003) PICK1, an anchoring protein that specifically targets protein Kinase Cα to mitochondria selectively upon serum stimulation in NIH 3T3 cells. The Journal of Biological Chemistry, 278(39), 37705-37712.

[78]   Wang, W.L., Yeh, S.F., Huang, E.Y.K., Lu, Y.L. and Wang, C.F. (2007) Mitochondrial anchoring of PKCα by PICK1 confers resistance to etoposide-induced apoptosis. Apoptosis, 12(10), 1857-1871.

[79]   Meinhardt, A. and Wilhelm, B., Seitz, J. (1999) Expression of mitochondria marker proteins during spermatogenesis. Human Reproduction Update, 5(2), 108-119.

[80]   Solakidi, S., Psarra, A.M., Nikolaropoulos, S. and Sekeris, C.E. (2005) Estrogen receptors α and β (ERα and ERβ) and androgen receptor (AR) in human sperm: localization of ERβ and AR in mitochondria of the midpiece. Human Reproduction, 20(12), 3481-3487.

[81]   Cardullo, R.A. and Baltz, J.M. (1991) Metabolic regulation in mammalian sperm: mitochondrial volume determines sperm length and flagellar beat frequency. Cell Motility and the Cytoskeleton, 19(3), 180-188.

[82]   Tombes, R.M. and Shapiro, B.M. (1985) Metabolite channeling: A phosphorylcreatine shuttle to mediate high energy phosphate transport between sperm mitochondrion and tail. Robert M. Cell, 41(1), 325-334.

[83]   Malo, A.F., Gomendio, M., Garde, J., Lang-Lenton, B., Soler, A.J. and Roldan, E.R. (2006) Sperm design and sperm function. Biology Letters, 2(2), 246-249.

[84]   Shi, L.Z., Nascimento, J.M., Chandsawangbhuwana, C., Botvinick, E.L. and Berns, M.W. (2008) An automatic system to study sperm motility and energetics. Biomedical Microdevices, 10(4), 573-583.

[85]   Nascimento, J.M., Shi, L.Z., Tam, J., Chandsawangbhuwana, C., Durrant, B., Botvinick, E.L. and Berns, M.W. (2008) Comparison of glycolysis and oxidative phosphorylation as energy sources for mammalian sperm motility, using the combination of fluorescence imaging, laser tweezers, and real-time automated tracking and trapping. Journal of Cellular Physiology, 217(3), 745-751.

[86]   Ho, H.C., Granish, K.A. and Suarez, S.S. (2002) Hyperactivated motility of bull sperm is triggered at the axoneme by Ca2+ and not cAMP. Developmental Biology, 250(1), 208-217.

[87]   Turner, R.M. (2003) Tales from the tail: What do we really know about sperm motility? Journal of Andrology, 24(6), 790-803.

[88]   Ishijima, S., Mohri, H., Overstreet, J.W. and Yudin, A.I. (2006) Hyperactivation of monkey spermatozoa is triggered by Ca2+ and Completed by cAMP. Molecular Reproduction and Development, 73(9), 1129-1139.

[89]   Zitta, K., Albrecht, M., Weidinger, S., Mayerhofer, A. and Köhn, F. (2007) Protease activated receptor 2 and epidermal growth factor receptor are involved in the regulation of human sperm motility. Asian Journal of Andrology, 9(5), 690-696.

[90]   Ashizawa, K., Omura, Y., Katayama, S., Tatemoto, H., Narumi, K. and Tsuzuki, Y. (2009) Intracellular signal transduction pathways in the regulation of fowl sperm motility: Evidence for the involvement of phosphatidylinositol 3-Kinase (PI3-K) cascade. Molecular Reproduction and Development, 76(7), 603-610.

[91]   Hershko, A. and Ciechanover, A. (1998) The ubiquitin system. Annual Review of Biochemistry, 67, 425-479.

[92]   Ciechanover, A., Orian, A. and Schwartz, A.L. (2000) Ubiquitin-mediated proteolysis: Biological regulation via destruction. Bioessays, 22(5), 442-451.

[93]   Ciechanover, A. and Iwai, K. (2004) The ubiquitin system: From basic mechanisms to the patient bed. IUBMB Life, 56(5), 193-201.

[94]   Mukhopadhyay, D. and Riezman, H. (2007) Proteosome- independent functions of ubiquitin in endocytosis and signaling. Science, 315(5809), 201-205.

[95]   Thompson, W.E., Ramalho-Santos, J. and Sutovsky, P. (2003) Ubiquitination of prohibitin in mammalian sperm mitochondria: Possible roles in the regulation of mitochondrial inheritance and sperm quality control. Biology of Reproduction, 69(1), 254-260.

[96]   Mundy, A.J., Ryder, T.A. and Edmonds, D.K. (1995) Asthenozoospermia and the human sperm mid-piece. Human Reproduction, 10(1), 116-119.

[97]   Folgerq, T., Bertheussen, K., Lindal, S., Torbergsen, T. and Oian, P. (1993) Mitochondrial disease and reduced sperm motility. Human Reproduction, 8(11), 1863-1868.

[98]   Spiropoulos, J., Turnbull, D.M. and Chinnery, P.F. (2002) Can mitochondrial DNA mutations cause sperm dysfunction? Molecular Human Reproduction, 8(8), 719-721.

[99]   St John, J.C., Jokhi, R.P. and Barratt, C.L. (2005) The impact of mitochondrial genetics on male infertility. International Journal of Andrology, 28(2), 65-73.

[100]   Shamsi, M.B., Kumar, R., Bhatt, A., Bamezai, R.N., Kumar, R., Gupta, N.P., Das, T.K. and Dada, R. (2008) Mitochondria DNA mutations in etiopathogenesis of male infertility. Indian Journal of Urology, 24(2), 150- 154.

[101]   St John, J.C., Sakkas, D. and Barratt, C.L. (2000) A role for mitochondrial DNA and sperm survival. Journal of Andrology, 21(2), 189-199.

[102]   Yan, W. (2009) Male infertility caused by spermiogenic defects: Lessons from gene knockouts. Molecular and Cellular Endocrinology, 306(1-2), 24-32.

[103]   St John, J.C., Jokhi, R.P. and Barratt, C.L. (2001) Men with oligoasthenoteratozoospermia harbour higher num- bers of multiple mitochondrial DNA deletions in their spermatozoa, but individual deletions are not indicative of overall aetiology. Molecular Human Reproduction, 7(1), 103-111.

[104]   Lanzafame, F.M., La Vignera, S., Vicari, E. and Calogero, A.E. (2009) Oxidative stress and medical antioxidant treatment in male infertility. Reproductive Biomedicine Online, 19(5), 638-659.

[105]   Latchoumycandane, C., Chitra, K.C. and Mathur, P.P. (2002). The effect of 2, 3, 7, 8-tetrachlorodibenzo-p- dioxin on the antioxidant system in mitochondrial and microsomal fractions of rat testis. Toxicology, 171(2-3), 127-135.

[106]   Tavares, R.S., Martins, F.C., Oliveira, P.J., Ramalho-Santos, J. and Peixoto, F.P. (2008) Parabens in male infertility—Is there a mitochondrial connection? Reproductive Toxicology, 27(1), 1-7.