Energetica cellulare Energia libera e mitocondri Origine endosimbiontica di mitocondri e plastidi Origine endosimbiontica di mitocondri e plastidi Produzione aerobica e anaerobica di ATP Il Mitocondrio Il Mitocondrio Il ciclo di Krebs: produzione di coenzimi ridotti Il ciclo di Krebs: produzione di coenzimi ridotti Trasportatori della membrana interna Mitocondri e perossisomi nel catabolismo degli acidi grassi Il catabolismo del glucosio è regolato allostericamente La forza lavoro attraverso la membrana interna Control 250 µM DA Colorazione con MitoTracker Red CMXRos La catena respiratoria La catena respiratoria CoQ-Citocromo c reduttasi Citocromo c ossidasi Sintesi di ATP Sintesi di ATP Trasportatori della membrana interna Mitocondri come depositi di calcio Local ER–mitochondria interactions. A representation is depicted of ER– mitochondria relationships and of some of the proteins involved in the cross-talk between the organelles. Ca2+ released from the ER through Ins(1,4,5)P3Rs is taken up by mitochondria through the MCU. Within mitochondria, Ca2+ modulates mitochondrial dehydrogenase activity and thus ATP production. Moreover, mitochondrial Ca2+ uptake regulates the spatio-temporal pattern of the cytosolic Ca2+ signal and, therefore, many Ca2+-dependent cellular processes. Massive and/or a prolonged accumulation of Ca2 in the mitochondria can lead to the opening of the PTP in the IMM and swelling of the organelle or, acting on mitochondria-shaping proteins [DRP-1, hFis1, OPA1, mitofusins (MFNs)], to mitochondrial cristae remodeling and modulation of apoptosis. The ‘in concert’ action of the two organelles in cell death is further supported by the presence on both the ER membrane and the OMM of different components of the Blc-2 family that have either a pro- (BIK, BAX, BAK) or an anti-apoptotic role (Bcl-2, Bcl-XL). ER and mitochondria could be linked physically at specific sites by cytoplasmic molecules (grp75, PACS-2), either directly or through proteins expressed on the two membranes (IP3R, VDAC). Readers are referred to the text for further details. CsmtDHs, Ca2+ sensitive mitochondrial dehydrogenases; Cyt c, cytochrome c; IMM, inner mitochondrial membrane; IP3R, inositol 1,4,5-trisphosphate receptor; OMM, outer mitochondrial membrane; MCU, mitochondrial Ca2+ uniporter; PTP, permeability transition pore; SERCA, sarcoplasmic-endoplasmic reticulum Ca2+ ATPase; VDAC, voltage-dependent anion channel. Mitocondri, calcio e apoptosi Poro di transizione mitocondriale Mitochondrial life cycle van der Bliek A M et al. Cold Spring Harb Perspect Biol 2013;5:a011072 ©2013 by Cold Spring Harbor Laboratory Press Controllo di qualità Kornmann B. Quality control in mitochondria: use it, break it, fix it, trash it. F1000Prime Rep. 2014 Mar 3;6:15. eCollection 2014. Review. PubMed PMID: 24669296; PubMed Central PMCID: PMC3944741. Fusione e fissione Otera H, Ishihara N, Mihara K. New insights into the function and regulation of mitochondrial fission. Biochim Biophys Acta. 2013; 1833:1256-68. doi: 10.1016/j.bbamcr.2013.02.002. Fusione e fissione Mitocondri e Autofagia Wild & Dikic, Nature Cell Biology 12, 104 - 106 (2010) Processamento proteolitico di PINK1 nei mitocondri polarizzati Degradazione PINK1 ad opera di una proteasi MG132sensibile (Jin & Youle, 2012) 29 Accumulo della forma nativa di PINK1 nei mitocondri depolarizzati PINK1 c (Jin & Youle, 2012) 30 Le proteine PINK1/Parkina mediano la mitofagia dei mitocondri danneggiati 31