The Transmembrane Segment of Tom20 Is Recognized by Mim1 for Docking to the Mitochondrial TOM Complex

Hulett, Joanne M; Lueder, Franziska B; Chan, Nickie C.; Perry, Andrew; Wolynec, P. Peter; Likić, Vladimir A; Gooley, Paul R.; Lithgow, Trevor

doi:10.1016/j.jmb.2007.12.021

Cited by 91 publications

(78 citation statements)

References 58 publications

(73 reference statements)

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“…Mim1 has been shown to be involved in the import and assembly of several a-helical outer membrane proteins [8][9][10][11][12]. Mitochondria lacking Mim1 were moderately affected in import and membrane integration of [ 35 S]Om45 (Fig 4A; Supplementary Fig S4A).…”

Section: Mim1-dependent Assembly Of Om45mentioning

confidence: 99%

The presequence pathway is involved in protein sorting to the mitochondrial outer membrane

et al. 2014

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The mitochondrial outer membrane contains integral a-helical and b-barrel proteins that are imported from the cytosol. The machineries importing b-barrel proteins have been identified, however, different views exist on the import of a-helical proteins. It has been reported that the biogenesis of Om45, the most abundant signal-anchored protein, does not depend on proteinaceous components, but involves direct insertion into the outer membrane. We show that import of Om45 occurs via the translocase of the outer membrane and the presequence translocase of the inner membrane. Assembly of Om45 in the outer membrane involves the MIM machinery. Om45 thus follows a new mitochondrial biogenesis pathway that uses elements of the presequence import pathway to direct a protein to the outer membrane.

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Section: Mim1-dependent Assembly Of Om45mentioning

confidence: 99%

The presequence pathway is involved in protein sorting to the mitochondrial outer membrane

et al. 2014

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“…Insertion of N-terminally anchored proteins, such as Tom20 and Tom70, is facilitated by the outer membrane insertase Mim1 (61)(62)(63). It remains unknown whether a protein-based machinery exists for the insertion of C-terminally anchored (tail-anchored) proteins into the outer membrane.…”

Section: Specific Transport Pathways and Their Interplays With Major mentioning

confidence: 99%

Mitochondrial protein homeostasis

2013

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Mitochondria use 800-1,500 proteins to perform their biological functions in the eukaryotic cells. Distinct transport and sorting mechanisms are responsible for the delivery of proteins to the correct location within mitochondria. Mitochondrial proteins undergo processing events and form functional assemblies.Finally, non-functional proteins are cleared to maintain healthy mitochondria. We provide an overview of the processes collectively contributing to the maintenance of mitochondrial protein homeostasis, which is critical for cell physiology and survival.

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“…The cytosolic domain of Tom22 mediates protein translocation and import of mitochondrial proteins (15)(16)(17)(18), where its negatively charged acid-rich region may interact with the polar surfaces of amphipathic presequences. Tom22 is a C-terminal tail-anchored protein in the mitochondrial outer membrane, and the cytosolic N-terminal domain collaborates with Tom20 to promote protein import (19)(20)(21)(22)(23). This led us to hypothesize that the residues present at the IMS side may mediate interaction with steroidogenic enzymes.…”

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confidence: 99%

An Outer Mitochondrial Translocase, Tom22, Is Crucial for Inner Mitochondrial Steroidogenic Regulation in Adrenal and Gonadal Tissues

Rajapaksha

Kaur

Prasad

et al. 2016

Molecular and Cellular Biology

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dAfter cholesterol is transported into the mitochondria of steroidogenic tissues, the first steroid, pregnenolone, is synthesized in adrenal and gonadal tissues to initiate steroid synthesis by catalyzing the conversion of pregnenolone to progesterone, which is mediated by the inner mitochondrial enzyme 3␤-hydroxysteroid dehydrogenase 2 (3␤HSD2). We report that the mitochondrial translocase Tom22 is essential for metabolic conversion, as its knockdown by small interfering RNA (siRNA) completely ablated progesterone conversion in both steroidogenic mouse Leydig MA-10 and human adrenal NCI cells. Tom22 forms a 500-kDa complex with mitochondrial proteins associated with 3␤HSD2. Although the absence of Tom22 did not inhibit mitochondrial import of cytochrome P450scc (cytochrome P450 side chain cleavage enzyme) and aldosterone synthase, it did inhibit 3␤HSD2 expression. Electron microscopy showed that Tom22 is localized at the outer mitochondrial membrane (OMM), while 3␤HSD2 is localized at the inner mitochondrial space (IMS), where it interacts through a specific region with Tom22 with its C-terminal amino acids and a small amino acid segment of Tom22 exposed to the IMS. Therefore, Tom22 is a critical regulator of steroidogenesis, and thus, it is essential for mammalian survival. Mitochondrial function is not limited to oxidative phosphorylation, as mitochondria are the site of steroid synthesis in specialized cells. Most mitochondrial proteins are expressed by nuclear genes with the mitochondrial targeting information in the mature protein. For example, some inner mitochondrial matrix (IMM) proteins have an internal, positively charged "presequence"-like signal, often preceded by a hydrophobic sequence (1), which leads to the arrest of translocation in the IMM and the subsequent lateral release of the protein into the lipid phase of the membrane (2). Import and subsequent intramitochondrial sorting of mitochondrial proteins are mediated by the mitochondrial membrane protein translocases. The translocase complexes in the outer mitochondrial membrane (OMM) are not tightly linked with those of the IMM; yet, they dynamically cooperate to achieve protein delivery to each mitochondrial subcompartment. To understand the mechanism of protein transport by the mitochondrial import/sorting system, it is essential to monitor and analyze the dynamic interactions among the constituents of the system. Steroidogenic cells do not store steroid hormone; therefore, an immediate steroidogenic response requires rapid synthesis of new steroid. Cholesterol mitochondrial transport initiates inner mitochondrial metabolic activity in steroidogenic cells within adrenal and gonadal tissues as well as the brain. Conversion of the first steroid, pregnenolone, to progesterone is catalyzed by 3␤-hydroxysteroid dehydrogenase 2 (3␤HSD2). Due to its central role in steroidogenesis, changes in 3␤HSD2 activity can have a wide range of effects, including hypertension, salt wasting crisis, and impaired sexual development (3-7). We have also identified p...

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The Transmembrane Segment of Tom20 Is Recognized by Mim1 for Docking to the Mitochondrial TOM Complex

Cited by 91 publications

References 58 publications

The presequence pathway is involved in protein sorting to the mitochondrial outer membrane

The presequence pathway is involved in protein sorting to the mitochondrial outer membrane

Mitochondrial protein homeostasis

An Outer Mitochondrial Translocase, Tom22, Is Crucial for Inner Mitochondrial Steroidogenic Regulation in Adrenal and Gonadal Tissues

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