Journal of Reproductive Immunology 83 (2009) 14–18 Contents lists available at ScienceDirect Journal of Reproductive Immunology journal homepage: www.elsevier.com/locate/jreprimm The role of mitochondrial proteins in sperm capacitation S. Shivaji * , Venkatesh Kota, Archana B. Siva Centre for Cellular and Molecular Biology, Uppal Road, Hyderabad 500007, India article info Article history: Received 24 December 2008 Received in revised form 6 August 2009 Accepted 25 August 2009 Keywords: Capacitation Mitochondria Tyrosine phosphorylation abstract Spermatozoa deposited in the female reproductive tract need to undergo a multifaceted maturation process prior to fertilization termed “capacitation”. This process is regulated by several proteins which are compartmentalized in discrete domains of the spermato- zoon including the head, the mid-piece and the principal piece. Over the last decade many proteins involved in capacitation have been identified, such as proteins involved in the organization of the tail, proteins involved in signal transduction, chaperones, ion-channel proteins and mitochondria-associated proteins. This review focuses on the identity and function of mitochondrial proteins which undergo capacitation-dependent tyrosine phos- phorylation in spermatozoa. © 2009 Elsevier Ireland Ltd. All rights reserved. 1. Introduction Mutations in the mitochondrial genome have been reported in infertile men, indicating that mitochondrial respiration defects contribute to male infertility. In fact, mice with a 4696 bp deletion in the mitochondrial DNA (mtDNA) are oligospermic and asthenozoospermic (Nakada et al., 2006) and motility of mammalian sperma- tozoa is impaired if oxidative phosphorylation is affected (Ruiz-Pesini et al., 2000) or if ATP synthesis is affected in the mitochondria (Halangk and Bohnensack, 1986). Glycol- ysis, in the principal piece of the flagellum is yet another source of ATP for spermatozoa and has been shown to be essential for sperm motility, hyperactivation and pro- tein tyrosine phosphorylation in the rhesus monkey (Hung et al., 2008). But, contradictory reports indicate that this alternative source may not be crucial, because sperm were able to sustain motility under conditions when glycolysis was inhibited (Ford, 2006). Therefore the age-old ques- tion as to what is the source of energy for sperm function, remains unanswered. While attempting to resolve this * Corresponding author. Tel.: +91 40 27192504; fax: +91 40 27160311. E-mail address: shivas@ccmb.res.in (S. Shivaji). long-standing issue, attention needs to be directed not only towards the source of energy generation and its correlation with motility, but also to other sperm functions such as hyperactivation, acrosome reaction and tyrosine phospho- rylation, the important hallmarks of sperm capacitation. Understanding the role of these phosphotyrosine proteins with respect to their influence on the hallmarks of capac- itation is essential in order to unravel the molecular basis of capacitation. 2. Signaling pathways involved in capacitation The signaling pathway involving cAMP-dependent protein tyrosine phosphorylation is unique to sperm capac- itation and studies have indicated that activity of protein kinase A (PKA) is essential for sperm tyrosine phospho- rylation, hyperactivation, and acrosome reaction (Lefievre et al., 2002). PKA influences tyrosine phosphorylation by regulating protein tyrosine kinases like src kinase (Varano et al., 2008). The other kinases that have been implicated in capacitation include protein kinase C (PKC), extracellu- lar signal regulated kinase (ERK1), the mitogen activated protein kinase (MAPK), phosphoinositide 3-kinase (PI3K) and protein kinase B (PKB/Akt) (Naor and Breitbart, 1997; Luconi et al., 2001). 0165-0378/$ – see front matter © 2009 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.jri.2009.08.009