Mitochondrial Membranes Restitution Proceeds via Vesicular Import from ER and Cytosol. Counterparts’ Resemblances and Variances in Mitochondria and Golgi Pathways

Abstract

The processes of mitochondrial restitution are controlled by nuclear genes that encode proteins synthesized in ER and cytosol and delivered as organelleand membrane-specific transport vesicles. The analysis of the transporters recovered from inner mitochondrial space (Mitosol) revealed that the ERsynthesized mitochondria-specific transport vesicles consist of two carriers, one remaining in outer mitochondrial membrane (OMM), and the other that transfers specific membrane segments to the inner mitochondrial membrane (IMM). The ER-assembled and IMM-committed membrane segments, while first integrated into OMM, undergo intra-mitochondrial lipid modification reflected in the synthesis of cardiolipin (CL) and inversion into Mitosol with load of IMM associated cytosolic proteins. Then, the CL-bedecked vesicles are released from OMM to Mitosol and upon contact with IMM fuse with the membrane, and the release of cytosolic cargo ensues. While ER-assembled mitochondria-specific transport vesicles fuse with OMM with the aid of the cytosolic, phosphatidylglycerol (PG)-specific phospholipase A 2 (PLA 2 ), the Mitosol-contained CL-specific PLA guides vesicles fusion with IMM. The described path of translocation of the membrane segments and the cytosol synthesized proteins into the designated mitochondrial compartments sustains growth and identity of OMM, IMM, maintains protein delivery for intramitochondrial lipid and protein modification in Mitosol, and ensures conformity of the cytosolic proteins cargo delivered to matrix.

The Flow of Information from Nucleus to Golgi Is Contingent upon Nuclear Membrane Synthesis and Protraction of the Ceramide-Containing Membrane to Endoplasmic Reticulum

“…Henceforward, we advance an idea that signal-controlled synchronized synthesis of lipids and proteins assemblies coordinately intercalate into the existing nuclear barrier, then the nucleus-determined membrane prototype exits to cytosol-exposed ER that completes orderly formation of the organelle and cell specific membranes [27] [28] [29]. This tenet of membrane biogenesis cannot be substituted or mimicked by an in vitro prepared lipid and protein assortments [23] [24], the process that never could replicate the precision of the in vivo step by step signal-controlled vesicular membrane assemblies delegated to Golgi and mitochondria transport pathways [28] [29] [30].…”