Influence of the mitochondrial outer membrane and the binding of creatine kinase to the mitochondrial inner membrane on the compartmentation of adenine nucleotides in the intermembrane space of rat heart mitochondria

1993 ◽  
Vol 1140 (3) ◽  
pp. 327-334 ◽  
Author(s):  
Frank N. Gellerich ◽  
Zaza A. Khuchua ◽  
Andrey V. Kuznetsov
Keyword(s):  
Creatine Kinase ◽  
Outer Membrane ◽  
Rat Heart ◽  
Adenine Nucleotides ◽  
Heart Mitochondria ◽  
Mitochondrial Outer Membrane ◽  
Intermembrane Space ◽  
Inner Membrane ◽  
Mitochondrial Inner Membrane ◽  
Rat Heart Mitochondria

scholarly journals Biogenesis of Mitochondrial Metabolite Carriers

Biomolecules ◽  
2020 ◽  
Vol 10 (7) ◽  
pp. 1008 ◽  
Author(s):  
Patrick Horten ◽  
Lilia Colina-Tenorio ◽  
Heike Rampelt
Keyword(s):  
Outer Membrane ◽  
Mitochondrial Outer Membrane ◽  
Intermembrane Space ◽  
Inner Membrane ◽  
Chaperone Function ◽  
Mitochondrial Inner Membrane ◽  
Metabolic Reactions ◽  
Almost All ◽  
Related Proteins ◽  
Shed Light

Metabolite carriers of the mitochondrial inner membrane are crucial for cellular physiology since mitochondria contribute essential metabolic reactions and synthesize the majority of the cellular ATP. Like almost all mitochondrial proteins, carriers have to be imported into mitochondria from the cytosol. Carrier precursors utilize a specialized translocation pathway dedicated to the biogenesis of carriers and related proteins, the carrier translocase of the inner membrane (TIM22) pathway. After recognition and import through the mitochondrial outer membrane via the translocase of the outer membrane (TOM) complex, carrier precursors are ushered through the intermembrane space by hexameric TIM chaperones and ultimately integrated into the inner membrane by the TIM22 carrier translocase. Recent advances have shed light on the mechanisms of TOM translocase and TIM chaperone function, uncovered an unexpected versatility of the machineries, and revealed novel components and functional crosstalk of the human TIM22 translocase.

scholarly journals Mitochondria Use Different Mechanisms for Transport of Multispanning Membrane Proteins through the Intermembrane Space

2003 ◽  
Vol 23 (21) ◽  
pp. 7818-7828 ◽  
Author(s):  
Ann E. Frazier ◽  
Agnieszka Chacinska ◽  
Kaye N. Truscott ◽  
Bernard Guiard ◽  
Nikolaus Pfanner ◽  
...  
Keyword(s):  
Outer Membrane ◽  
Heat Shock Protein 70 ◽  
Mitochondrial Outer Membrane ◽  
Intermembrane Space ◽  
Carrier Proteins ◽  
Inner Membrane ◽  
Tom Complex ◽  
Mitochondrial Inner Membrane ◽  
Integral Proteins ◽  
Matrix Heat

ABSTRACT The mitochondrial inner membrane contains numerous multispanning integral proteins. The precursors of these hydrophobic proteins are synthesized in the cytosol and therefore have to cross the mitochondrial outer membrane and intermembrane space to reach the inner membrane. While the import pathways of noncleavable multispanning proteins, such as the metabolite carriers, have been characterized in detail by the generation of translocation intermediates, little is known about the mechanism by which cleavable preproteins of multispanning proteins, such as Oxa1, are transferred from the outer membrane to the inner membrane. We have identified a translocation intermediate of the Oxa1 preprotein in the translocase of the outer membrane (TOM) and found that there are differences from the import mechanisms of carrier proteins. The intermembrane space domain of the receptor Tom22 supports the stabilization of the Oxa1 intermediate. Transfer of the Oxa1 preprotein to the inner membrane is not affected by inactivation of the soluble TIM complexes. Both the inner membrane potential and matrix heat shock protein 70 are essential to release the preprotein from the TOM complex, suggesting a close functional cooperation of the TOM complex and the presequence translocase of the inner membrane. We conclude that mitochondria employ different mechanisms for translocation of multispanning proteins across the aqueous intermembrane space.

scholarly journals Mitochondrial inner-membrane protease Yme1 degrades outer-membrane proteins Tom22 and Om45

2017 ◽  
Vol 217 (1) ◽  
pp. 139-149 ◽  
Author(s):  
Xi Wu ◽  
Lanlan Li ◽  
Hui Jiang
Keyword(s):  
Outer Membrane ◽  
Outer Membrane Proteins ◽  
Ubiquitin Proteasome System ◽  
Mitochondrial Outer Membrane ◽  
Intermembrane Space ◽  
Inner Membrane ◽  
Mitochondrial Proteome ◽  
Mitochondrial Inner Membrane ◽  
Ubiquitin Proteasome

Mitochondria are double-membraned organelles playing essential metabolic and signaling functions. The mitochondrial proteome is under surveillance by two proteolysis systems: the ubiquitin–proteasome system degrades mitochondrial outer-membrane (MOM) proteins, and the AAA proteases maintain the proteostasis of intramitochondrial compartments. We previously identified a Doa1–Cdc48-Ufd1-Npl4 complex that retrogradely translocates ubiquitinated MOM proteins to the cytoplasm for degradation. In this study, we report the unexpected identification of MOM proteins whose degradation requires the Yme1-Mgr1-Mgr3 i-AAA protease complex in mitochondrial inner membrane. Through immunoprecipitation and in vivo site-specific photo–cross-linking experiments, we show that both Yme1 adapters Mgr1 and Mgr3 recognize the intermembrane space (IMS) domains of the MOM substrates and facilitate their recruitment to Yme1 for proteolysis. We also provide evidence that the cytoplasmic domain of substrate can be dislocated into IMS by the ATPase activity of Yme1. Our findings indicate a proteolysis pathway monitoring MOM proteins from the IMS side and suggest that the MOM proteome is surveilled by mitochondrial and cytoplasmic quality control machineries in parallel.

Involvement of SH-groups during interaction of diazoxide with the inner membrane of rat heart mitochondria

2007 ◽  
Vol 415 (1) ◽  
pp. 206-210 ◽  
Author(s):  
S. M. Korotkov ◽  
V. P. Nesterov ◽  
L. V. Emel’yanova ◽  
N. N. Ryabchikov
Keyword(s):  
Rat Heart ◽  
Heart Mitochondria ◽  
Inner Membrane ◽  
Sh Groups ◽  
Rat Heart Mitochondria

scholarly journals Role of mitochondrial inner membrane organizing system in protein biogenesis of the mitochondrial outer membrane

2012 ◽  
Vol 23 (20) ◽  
pp. 3948-3956 ◽  
Author(s):  
Maria Bohnert ◽  
Lena-Sophie Wenz ◽  
Ralf M. Zerbes ◽  
Susanne E. Horvath ◽  
David A. Stroud ◽  
...  
Keyword(s):  
Outer Membrane ◽  
Early Stage ◽  
Outer Membrane Proteins ◽  
Mitochondrial Outer Membrane ◽  
Large Core ◽  
Large Protein ◽  
Inner Membrane ◽  
Mitochondrial Inner Membrane ◽  
Protein Biogenesis

Mitochondria contain two membranes, the outer membrane and the inner membrane with folded cristae. The mitochondrial inner membrane organizing system (MINOS) is a large protein complex required for maintaining inner membrane architecture. MINOS interacts with both preprotein transport machineries of the outer membrane, the translocase of the outer membrane (TOM) and the sorting and assembly machinery (SAM). It is unknown, however, whether MINOS plays a role in the biogenesis of outer membrane proteins. We have dissected the interaction of MINOS with TOM and SAM and report that MINOS binds to both translocases independently. MINOS binds to the SAM complex via the conserved polypeptide transport–associated domain of Sam50. Mitochondria lacking mitofilin, the large core subunit of MINOS, are impaired in the biogenesis of β-barrel proteins of the outer membrane, whereas mutant mitochondria lacking any of the other five MINOS subunits import β-barrel proteins in a manner similar to wild-type mitochondria. We show that mitofilin is required at an early stage of β-barrel biogenesis that includes the initial translocation through the TOM complex. We conclude that MINOS interacts with TOM and SAM independently and that the core subunit mitofilin is involved in biogenesis of outer membrane β-barrel proteins.

scholarly journals Role of the intermembrane-space domain of the preprotein receptor Tom22 in protein import into mitochondria.

1996 ◽  
Vol 16 (8) ◽  
pp. 4035-4042 ◽  
Author(s):  
D A Court ◽  
F E Nargang ◽  
H Steiner ◽  
R S Hodges ◽  
W Neupert ◽  
...  
Keyword(s):  
Outer Membrane ◽  
Protein Import ◽  
Protein Translocation ◽  
Specific Binding ◽  
Mitochondrial Outer Membrane ◽  
Intermembrane Space ◽  
Inner Membrane ◽  
Terminal Domain ◽  
Tom Complex

Tom22 is an essential component of the protein translocation complex (Tom complex) of the mitochondrial outer membrane. The N-terminal domain of Tom22 functions as a preprotein receptor in cooperation with Tom20. The role of the C-terminal domain of Tom22, which is exposed to the intermembrane space (IMS), in its own assembly into the Tom complex and in the import of other preproteins was investigated. The C-terminal domain of Tom22 is not essential for the targeting and assembly of this protein, as constructs lacking part or all of the IMS domain became imported into mitochondria and assembled into the Tom complex. Mutant strains of Neurospora expressing the truncated Tom22 proteins were generated by a novel procedure. These mutants displayed wild-type growth rates, in contrast to cells lacking Tom22, which are not viable. The import of proteins into the outer membrane and the IMS of isolated mutant mitochondria was not affected. Some but not all preproteins destined for the matrix and inner membrane were imported less efficiently. The reduced import was not due to impaired interaction of presequences with their specific binding site on the trans side of the outer membrane. Rather, the IMS domain of Tom22 appears to slightly enhance the efficiency of the transfer of these preproteins to the import machinery of the inner membrane.

scholarly journals Proteinase treatment of intact hepatic mitochondria has differential effects on inhibition of carnitine palmitoyltransferase by different inhibitors

1992 ◽  
Vol 282 (3) ◽  
pp. 909-914 ◽  
Author(s):  
K Kashfi ◽  
G A Cook
Keyword(s):  
Outer Membrane ◽  
Adenylate Kinase ◽  
Citrate Synthase ◽  
Physiological State ◽  
Carnitine Palmitoyltransferase ◽  
Mitochondrial Outer Membrane ◽  
Intermembrane Space ◽  
Mitochondrial Inner Membrane ◽  
Malonyl Coa ◽  
No Release

Proteolysis of intact mitochondria by Nagarse (subtilisin BPN') and papain resulted in limited loss of activity of the outer-membrane carnitine palmitoyltransferase, but much greater loss of sensitivity to inhibition by malonyl-CoA. In contrast with a previous report [Murthy & Pande (1987) Proc. Natl. Acad. Sci. U.S.A. 84, 378-382], we found that trypsin had no effect on malonyl-CoA sensitivity. Even when 80% of activity was destroyed by trypsin, there was no difference in the malonyl-CoA sensitivity of the enzyme remaining. Trypsin caused release of the intermembrane-space enzyme adenylate kinase, indicating loss of integrity of the mitochondrial outer membrane, whereas Nagarse and papain caused no release of that enzyme. Citrate synthase was not released by any of the three proteinases, indicating no damage to the mitochondrial inner membrane. When we examined the effects of proteolysis on the inhibition of carnitine palmitoyltransferase by a wide variety of inhibitors having different mechanisms of inhibition, we found differential proteolytic effects that were specific for those inhibitors (malonyl-CoA and hydroxyphenylglyoxylate) that have their inhibitory potencies diminished by changes in physiological state. Both of those inhibitors protected carnitine palmitoyltransferase from the effects of proteolysis, but did not inhibit the proteinases directly. Inhibition by two other inhibitors (DL-2-bromopalmitoyl-CoA and N-benzyladriamycin 14-valerate) was not altered by proteinase treatment, even when most of the enzyme activity had been destroyed. Inhibition by glyburide, which is minimally affected by physiological state, was affected only to a slight extent at the highest concentration of trypsin tested. Proteolysis by Nagarse appeared to produce loss of co-operativity in malonyl-CoA inhibition. The effects of proteolysis are discussed and compared with changes in Ki occurring with changing physiological states.

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