Hindawi Publishing Corporation International Journal of Cell Biology Volume 2012, Article ID 729290, 13 pages doi:10.1155/2012/729290 Review Article Mitochondrial Dynamics in Cancer and Neurodegenerative and Neuroinﬂammatory Diseases Mauro Corrado,1 Luca Scorrano,1, 2 and Silvia Campello3 1 University of Geneva, 1211 Geneva, Switzerland 2 Venetian Institute of Molecular Medicine, 35129 Padova, Italy 3 IRCCS Fondazione Santa Lucia, 00143 Rome, Italy Correspondence should be addressed to Luca Scorrano, luca.scorrano@unige.ch and Silvia Campello, s.campello@hsantalucia.it Received 6 March 2012; Accepted 12 April 2012 Academic Editor: Pier Giorgio Mastroberardino Copyright © 2012 Mauro Corrado et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Mitochondria are key organelles in the cell, hosting essential functions, from biosynthetic and metabolic pathways, to oxidative phosphorylation and ATP production, from calcium buﬀering to red-ox homeostasis and apoptotic signalling pathways. Mitochondria are also dynamic organelles, continuously fusing and dividing, and their localization, size and traﬃcking are ﬁnely regulated. Moreover, in recent decades, alterations in mitochondrial function and dynamics have been implicated in an increasing number of diseases. In this review, we focus on the relationship clariﬁed hitherto between mitochondrial dynamics and cancer, neurodegenerative and neuroinﬂammatory diseases. 1. Introduction In eukaryotic cells, the role of mitochondria is pivotal both in providing essential molecules and signals for life and in amplifying signals of death. In regard to the cell life, mitochondria produce most of the ATP necessary to the cell through oxidative phosphorylation, and they are involved, among the others, in TCA cycle, fatty acid metabolism, hemesynthesis, and gluconeogenesis. As regards the cell death, mitochondria are involved in Ca2+ and red- ox homeostasis, which are dysregulated during cell death, and they release proapoptotic proteins, such as cytochrome c, SMAC/DIABLO, AIF, Endo G, and Omi/HTRA2, after mito- chondrial membrane permeabilization and cristae remodel- ing [1–3]. Moreover, mitochondria are highly dynamic organelles that can fuse and divide, forming an interconnected network or fragmented units inside the cell, according to diﬀerent stimuli impinging on the fusion/ﬁssion machinery, repre- sented by the mitochondria shaping proteins: MFN1, MFN2, OPA1, regulators of fusion, and DRP1, FIS1, MFF, and MIEF1, which modulate ﬁssion [4] (see Figure 1(a)). 1.1. Mitochondrial Fusion. MFN1 and MFN2, two dynamin- related GTPases, are the main regulators of mitochon- drial fusion at the level of outer mitochondrial mem- brane (OMM). They can interact, forming homo- and heterodimers; after conformational changes led by the hydrolysis of GTP, they force the OMM to fuse [5]. Interestingly, MFN2 is also responsible for ER/mitochondria tethering with an important implication in Ca2+ home- ostasis and signalling [6]. OPA1, another dynamin-related GTPase, is located in the inner mitochondrial membrane (IMM) where, together with MFN1, it plays a role in controlling fusion at this level [7]. OPA1 has also a role in controlling cell-death; in fact, heterocomplexes between proteolytic processed or unprocessed forms of OPA1 reg- ulate the width of cristae junctions and the subsequent release of cytochrome c, which then interacts with APAF1 and caspase 9 forming the apoptosome, whose activation results in the ampliﬁcation of cell death signals [8, 9]. Other proteins have been linked to mitochondrial fusion, such as LETM1 [10], the Phospholipase D (PLD) [11], and Prohibitins (Phb) [12], the latter necessary for OPA1 processing.