ABSTRACT
Introduction .................................................................................................................................... 316 Mitochondrial Membrane Structure and Composition .................................................................. 317
Organization and Dynamics of Mitochondrial Membranes ...................................................... 317 The Molecular Basis of IM Morphology .................................................................................. 321 Interaction between Mitochondria and the ER Membrane ....................................................... 322 Functional Signi˜cance of the MAM-Mitochondria Interface ................................................. 323
The Role of the MAM in Ca2+ Signaling and Homeostasis ................................................. 324 The Role of the MAM in Lipid Synthesis and Traf˜cking .................................................. 324
Mechanisms of Mitochondrial Lipid Biogenesis ........................................................................... 324 The Lipid Composition of Mitochondria .................................................................................. 324 Mechanisms of Mitochondrial Lipid Transport ........................................................................ 325 Aminoglycerophospholipid Synthesis and Traf˜cking ............................................................. 327
Phosphatidylserine ............................................................................................................... 327 Phosphatidylethanolamine ................................................................................................... 329 Phosphatidylcholine ............................................................................................................. 329
CL Biosynthesis ........................................................................................................................ 330 Sterol Transport ......................................................................................................................... 331
Mechanisms of Mitochondrial Membrane Protein Biogenesis ...................................................... 332 Physical Principles of Membrane Protein Integration .............................................................. 333 Prokaryotic Membrane Protein Integration Complexes ............................................................ 334
Protein Transport and Integration at the Bacterial IM .......................................................... 334 The Biogenesis of Bacterial OM Proteins ............................................................................ 335
Mitochondrial Protein Translocation Systems: Overview ........................................................ 336 Targeting Proteins to the Mitochondrion .............................................................................. 336 Mitochondrial Protein Translocases ..................................................................................... 337
The Biogenesis of Mitochondrial OM Proteins ........................................................................ 341 Integration of β-Barrel Proteins: An Evolutionarily Conserved Mechanism ....................... 341 Integration of α-Helical Proteins: Diverse Mechanisms ...................................................... 343
The Biogenesis of Mitochondrial IM Proteins .......................................................................... 345 Integration of Polytopic Membrane Proteins with Internal Signal Sequences ..................... 345 Integration of Presequence-Containing Membrane Proteins ................................................ 347 Integration by the OXA Complex ........................................................................................ 350
Mitochondrial Membrane Protein Assembly ............................................................................ 351 The Choreography of TOM Complex Assembly ................................................................. 351
Mitochondria are the sites of several metabolic processes that are fundamental to eukaryotic cells including electron transport and oxidative phosphorylation (OXPHOS), the Krebs cycle, Ca2+ homeostasis, β-oxidation of fatty acids, and biogenesis of heme and Fe/S clusters. The central role that these organelles play in programmed cell death (apoptosis) [1], ageing [2], and cancer [3,4] has been the subject of extensive research in recent years.
