scholarly journals Dual Function of Sdh3 in the Respiratory Chain and TIM22 Protein Translocase of the Mitochondrial Inner Membrane

2011 ◽  
Vol 44 (5) ◽  
pp. 811-818 ◽  
Author(s):  
Natalia Gebert ◽  
Michael Gebert ◽  
Silke Oeljeklaus ◽  
Karina von der Malsburg ◽  
David A. Stroud ◽  
...  
Keyword(s):  
Respiratory Chain ◽  
Dual Function ◽  
Inner Membrane ◽  
Mitochondrial Inner Membrane

scholarly journals YME1L controls the accumulation of respiratory chain subunits and is required for apoptotic resistance, cristae morphogenesis, and cell proliferation

2012 ◽  
Vol 23 (6) ◽  
pp. 1010-1023 ◽  
Author(s):  
Lukas Stiburek ◽  
Jana Cesnekova ◽  
Olga Kostkova ◽  
Daniela Fornuskova ◽  
Kamila Vinsova ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Membrane Protein ◽  
Respiratory Chain ◽  
Integral Membrane Protein ◽  
Intermembrane Space ◽  
Wild Type ◽  
Inner Membrane ◽  
Mitochondrial Inner Membrane ◽  
Human Orthologue ◽  
Excessive Accumulation

Mitochondrial ATPases associated with diverse cellular activities (AAA) proteases are involved in the quality control and processing of inner-membrane proteins. Here we investigate the cellular activities of YME1L, the human orthologue of the Yme1 subunit of the yeast i‑AAA complex, using stable short hairpin RNA knockdown and expression experiments. Human YME1L is shown to be an integral membrane protein that exposes its carboxy-terminus to the intermembrane space and exists in several complexes of 600–1100 kDa. The stable knockdown of YME1L in human embryonic kidney 293 cells led to impaired cell proliferation and apoptotic resistance, altered cristae morphology, diminished rotenone-sensitive respiration, and increased susceptibility to mitochondrial membrane protein carbonylation. Depletion of YME1L led to excessive accumulation of nonassembled respiratory chain subunits (Ndufb6, ND1, and Cox4) in the inner membrane. This was due to a lack of YME1L proteolytic activity, since the excessive accumulation of subunits was reversed by overexpression of wild-type YME1L but not a proteolytically inactive YME1L variant. Similarly, the expression of wild-type YME1L restored the lamellar cristae morphology of YME1L-deficient mitochondria. Our results demonstrate the importance of mitochondrial inner-membrane proteostasis to both mitochondrial and cellular function and integrity and reveal a novel role for YME1L in the proteolytic regulation of respiratory chain biogenesis.

scholarly journals The translocator maintenance protein Tam41 is required for mitochondrial cardiolipin biosynthesis

2008 ◽  
Vol 183 (7) ◽  
pp. 1213-1221 ◽  
Author(s):  
Stephan Kutik ◽  
Michael Rissler ◽  
Xue Li Guan ◽  
Bernard Guiard ◽  
Guanghou Shui ◽  
...  
Keyword(s):  
Membrane Potential ◽  
Respiratory Chain ◽  
Matrix Protein ◽  
Mitochondrial Protein ◽  
Pleiotropic Effects ◽  
Mitochondrial Matrix ◽  
Carrier Proteins ◽  
Inner Membrane ◽  
Mitochondrial Inner Membrane

The mitochondrial inner membrane contains different translocator systems for the import of presequence-carrying proteins and carrier proteins. The translocator assembly and maintenance protein 41 (Tam41/mitochondrial matrix protein 37) was identified as a new member of the mitochondrial protein translocator systems by its role in maintaining the integrity and activity of the presequence translocase of the inner membrane (TIM23 complex). Here we demonstrate that the assembly of proteins imported by the carrier translocase, TIM22 complex, is even more strongly affected by the lack of Tam41. Moreover, respiratory chain supercomplexes and the inner membrane potential are impaired by lack of Tam41. The phenotype of Tam41-deficient mitochondria thus resembles that of mitochondria lacking cardiolipin. Indeed, we found that Tam41 is required for the biosynthesis of the dimeric phospholipid cardiolipin. The pleiotropic effects of the translocator maintenance protein on preprotein import and respiratory chain can be attributed to its role in biosynthesis of mitochondrial cardiolipin.

The Non-Ohmic Proton Leak—25 Years On

1997 ◽  
Vol 17 (3) ◽  
pp. 251-257 ◽  
Author(s):  
David G. Nicholls
Keyword(s):  
Ion Transport ◽  
Respiratory Chain ◽  
Atp Synthesis ◽  
Proton Leak ◽  
Protonmotive Force ◽  
Proton Conductance ◽  
Inner Membrane ◽  
Ohm’S Law ◽  
Mitochondrial Inner Membrane ◽  
Proton Current

The proton conductance of the mitochondrial inner membrane can be quantified by applying Ohm's law to the experimentally determined protonmotive force and the proton current flowing around the proton circuit in the absence of ATP synthesis or ion transport. This last parameter is derived from the rate of State 4 respiration multiplied by the H+/O stoichiometry for the substrate. When the activity of the dehydrogenase supplying electrons to the respiratory chain is progressively increased the proton conductance increases rapidly when the protonmotive force is greater than 220 mV. The consequences of this non-ohmic relationship are discussed.

scholarly journals The Metalloprotease Encoded by ATP23 Has a Dual Function in Processing and Assembly of Subunit 6 of Mitochondrial ATPase

2007 ◽  
Vol 18 (2) ◽  
pp. 617-626 ◽  
Author(s):  
Xiaomei Zeng ◽  
Walter Neupert ◽  
Alexander Tzagoloff
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Dual Function ◽  
Mitochondrial Atpase ◽  
Null Mutant ◽  
Extra Copy ◽  
Inner Membrane ◽  
Mitochondrial Inner Membrane ◽  
Processing Activity ◽  
Subunit 9

In the present study we have identified a new metalloprotease encoded by the nuclear ATP23 gene of Saccharomyces cerevisiae that is essential for expression of mitochondrial ATPase (F1-FO complex). Mutations in ATP23 cause the accumulation of the precursor form of subunit 6 and prevent assembly of FO. Atp23p is associated with the mitochondrial inner membrane and is conserved from yeast to humans. A mutant harboring proteolytically inactive Atp23p accumulates the subunit 6 precursor but is nonetheless able to assemble a functional ATPase complex. These results indicate that removal of the subunit 6 presequence is not an essential event for ATPase biogenesis and that Atp23p, in addition to its processing activity, must provide another important function in FO assembly. The product of the yeast ATP10 gene was previously shown to interact with subunit 6 and to be required for its association with the subunit 9 ring. In this study one extra copy of ATP23 was found to be an effective suppressor of an atp10 null mutant, suggesting an overlap in the functions of Atp23p and Atp10p. Atp23p may, therefore, also be a chaperone, which in conjunction with Atp10p mediates the association of subunit 6 with the subunit 9 ring.

scholarly journals Selective and Reversible Disruption of Mitochondrial Inner Membrane Protein Complexes by Lipophilic Cations

2021 ◽  
Author(s):  
Anezka Kafkova ◽  
Lisa Tilokani ◽  
Filip Trčka ◽  
Veronika Šrámková ◽  
Marie Vancová ◽  
...  
Keyword(s):  
Membrane Protein ◽  
Respiratory Chain ◽  
Mitochondrial Membrane ◽  
Mitochondrial Morphology ◽  
Respiratory Chain Complexes ◽  
Inner Membrane ◽  
Protein Levels ◽  
Mitochondrial Inner Membrane ◽  
Chain Complexes ◽  
The Impact

ABSTRACTMitochondria represent an attractive drug target in the treatment of many diseases. One of the most commonly used approaches to deliver therapeutics specifically into mitochondria is their conjugation to the triphenylphosphonium (TPP) moiety. While the TPP molecule is often regarded as biologically inert, there is evidence that the moiety itself has a significant impact on the activity of mitochondrial respiratory chain complexes.We studied the impact of a subchronic exposure of C2C12 mouse myoblasts to a set of TPP derivatives. Our results show that the alkyl-TPP cause dose- and hydrophobicity-dependent alterations of mitochondrial morphology and a selective decrease in the amounts of mitochondrial inner membrane (but not outer membrane) proteins including structural subunits of the respiratory chain complexes (such as MT-CO1 of complex IV or NDUFB8 of complex I), as well as components of the mitochondrial calcium uniporter complex (MCUC). The treatment with alkyl-TPP additionally resulted in OPA1-cleavage. Both the structural and functional effects of alkyl-TPP were found to be reversible. A similar effect was observed with the mitochondria-targeted antioxidant MitoQ. We further show that this effect on protein levels cannot be explained solely by a decrease in mitochondrial membrane potential.We conclude that TPP derivatives negatively affect mitochondrial structure and function at least in part through their effect on selective mitochondrial membrane protein levels via a reversible controlled process.

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