As the central component of the complement system, C3 influences susceptibility to infectious and febrile episodes during infancy. Hence C3 could indirectly modulate susceptibility to FS, whether simple or complex. The complement Trichostatin A system might also play a role in the developing nervous system by tagging unwanted synapses for elimination. Inter-individual variations of C3 expression during brain development would then influence the building of neuronal circuits and the labeling of imprecise connections, hence favoring future susceptibility to seizures and epilepsy. Later in life, MTLE pathogenesis might also involve the reactivation of such developmental and complement-dependent remodeling pathways, while the complement system and C3 particularly, may also trigger neuroprotective effects during the latency period of MTLE. Overall C3-dependent susceptibility to FS and to MTLE-FS+ might rely on a very precise albeit evolving balance between beneficial and detrimental effects of the complement system. Studies to date have associated PHB1 with diverse roles in the maintenance of cellular homeostasis. Initial work suggested it functions as an inhibitor of DNA synthesis, a role which was later assigned to its 39UTR. A T-allelic expression form of PHB1 was associated with an increased risk of breast cancer ; however this association was not confirmed in a clinical setting. PHB1 co-localizes with transcription factors of the E2F family in the nucleus of breast carcinoma cells, and interacts with the Rb tumor suppressor protein pRB in the nucleus resulting in inhibition of the cell cycle. Correspondingly, siRNA-mediated silencing of PHB1 expression was found to increase breast cancer cell proliferation. Despite these indications of a tumor suppressor activity, recent studies have also demonstrated reduced cell proliferation upon loss of PHB1 expression in mouse embryonic fibroblasts and other primary cells; and the rescue of cell proliferation upon overexpression of mitochondrial-targeted PHB2. Our recent work indicates PHB1 also plays a role in cell migration: Transient silencing of PHB1 by siRNA-mediated knockdown led to a clumping phenotype in HeLa cells, comparable to that of a Her2/ErbB2 or Rac defect, i.e. clumped cells showed marked membrane staining for pan-cadherin and b-catenin. The authors suggested contact between cells were disrupted in tumor cells due to the loss of PHB1. Studies in yeast have consistently shown that PHB1 and PHB2 act as mitochondrial chaperones in the inner mitochondrial membrane. PHB1 and PHB2 are interdependent on the protein level and loss of one simultaneously leads to the loss of the other. They interact with mitochondrial proteases, particularly mAAA, which is required in the assembly of respiratory chain complexes. A knock-out of prohibitins in yeast led to a reduced replicative lifespan and a defect in mitochondrial membrane potential. Several recent studies have also addressed the mitochondrial function of prohibitins in human cell lines: Overexpression of PHB1 was found to protect against oxidative stress.