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Identification of a Dynamic Mitochondrial Protein Complex Driving Cholesterol Import, Trafficking, and Metabolism to Steroid Hormones
Open accessAbstract
Steroid hormones are critical for organismal development and health. The rate-limiting step in steroidogenesis is the transport of cholesterol from the outer mitochondrial membrane (OMM) to the cytochrome P450 enzyme CYP11A1 in the inner mitochondrial membrane (IMM). Cholesterol transfer occurs through a complex termed the "transduceosome," in which cytosolic steroidogenic acute regulatory protein interacts with OMM proteins translocator protein and voltage-dependent anion channel (VDAC) to assist with the transfer of cholesterol to OMM. It has been proposed that cholesterol transfer from OMM to IMM occurs at specialized contact sites bridging the two membranes composed of VDAC and IMM adenine nucleotide translocase (ANT). Blue native PAGE of Leydig cell mitochondria identified two protein complexes that were able to bind cholesterol at 66- and 800-kDa. Immunoblot and mass spectrometry analyses revealed that the 800-kDa complex contained the OMM translocator protein (18-kDa) and VDAC along with IMM CYP11A1, ATPase family AAA domain-containing protein 3A (ATAD3A), and optic atrophy type 1 proteins, but not ANT. Knockdown of ATAD3A, but not ANT or optic atrophy type 1, in Leydig cells resulted in a significant decrease in hormone-induced, but not 22R-hydroxycholesterol-supported, steroid production. Using a 22-phenoxazonoxy-5-cholene-3-beta-ol CYP11A1-specific probe, we further demonstrated that the 800-kDa complex offers the microenvironment needed for CYP11A1 activity. Addition of steroidogenic acute regulatory protein to the complex mobilized the cholesterol bound at the 800-kDa complex, leading to increased steroid formation. These results identify a bioactive, multimeric protein complex spanning the OMM and IMM unit that is responsible for the hormone-induced import, segregation, targeting, and metabolism of cholesterol.
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“This CYP11A1 metabolon model integrates with work on the steroidogenic transduceosome, a multiprotein complex traversing the OMM and IMM of the steroidogenic mitochondria integrating the movement of cholesterol with intracellular signaling to CYP111A1 (90, 91) (Figure 5).”
From Adrenal Mitochondria and Steroidogenesis: From Individual Proteins to Functional Protein Assemblies (2016) · cites this paper as [90]
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“ATAD3A appears capable of homooligomerization, and as noted above, appears to be a partner protein in the mitochondrial transduceosome of steroidogenic cells, critical for cholesterol import into mitochondria and steroidogenesis (90, 145).”
From Adrenal Mitochondria and Steroidogenesis: From Individual Proteins to Functional Protein Assemblies (2016) · cites this paper as [90]
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“In addition, these natively isolated CYP11A1 complexes were functionally active, cleaving the aliphatic tail of a fluorescent cholesterol reporter.”
From Adrenal Mitochondria and Steroidogenesis: From Individual Proteins to Functional Protein Assemblies (2016) · cites this paper as [90]
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“However, examination of native protein complexes in steroidogenic mitochondria from tumor Leydig cells using BN-PAGE and mass spectroscopy suggested that CYP11A1 and FDXR physically associate (90).”
From Adrenal Mitochondria and Steroidogenesis: From Individual Proteins to Functional Protein Assemblies (2016) · cites this paper as [90]
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“The TSPO–VDAC platform appears to serve as an OMM base for the steroidogenic transduceosome cholesterol-transfer machinery (90, 91), a complex which appears to predominantly contain the polymerized form of TSPO (90).”
From Adrenal Mitochondria and Steroidogenesis: From Individual Proteins to Functional Protein Assemblies (2016) · cites this paper as [90]
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Citations
Cites
Close Contacts with the Endoplasmic Reticulum as Determinants of Mitochondrial Ca 2+ Responses
Rizzuto, R., Pinton, P., Carrington, W., Fay, F. S., Fogarty, K. E., Lifshitz, L. M., Tuft, R. A., & Pozzan, T. (1998) · Science · doi:10.1126/science.280.5370.1763 · Cited by 2,257
RAS–RAF–MEK-dependent oxidative cell death involving voltage-dependent anion channels
Yagoda, N., von Rechenberg, M., Zaganjor, E., Bauer, A. J., Yang, W. S., Fridman, D. J., Wolpaw, A. J., Smukste, I., Peltier, J. M., Boniface, J. J., et al. (2007) · Nature · doi:10.1038/nature05859 · Cited by 1,631
Mitochondrial Transport of Cations: Channels, Exchangers, and Permeability Transition
Bernardi, P. (1999) · Physiological Reviews · doi:10.1152/physrev.1999.79.4.1127 · Cited by 1,546
Isozymes of mammalian hexokinase: structure, subcellular localization and metabolic function
Wilson, J. E. (2003) · Journal of Experimental Biology · doi:10.1242/jeb.00241 · Cited by 1,085
Complexes of sequential metabolic enzymes
Srere, P. A. (1987) · Annual Review of Biochemistry · doi:10.1146/annurev.bi.56.070187.000513 · Cited by 1,058
Respiratory active mitochondrial supercomplexes
Acín-Pérez, R., Fernández-Silva, P., Peleato, M. L., Pérez-Martos, A., & Enriquez, J. A. (2008) · Molecular Cell · doi:10.1016/j.molcel.2008.10.021 · Cited by 817
McEnery, M. W., Snowman, A. M., Trifiletti, R. R., & Snyder, S. H. (1992) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.89.8.3170 · Cited by 708
Rone, M. B., Fan, J., & Papadopoulos, V. (2009) · Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids · doi:10.1016/j.bbalip.2009.03.001 · Cited by 399
Self-citationRapid regulation of steroidogenesis by mitochondrial protein import
Bose, H. S., Lingappa, V. R., & Miller, W. L. (2002) · Nature · doi:10.1038/417087a · Cited by 357
Minireview: Regulation of Steroidogenesis by Electron Transfer
Miller, W. L. (2005) · Endocrinology · doi:10.1210/en.2005-0096 · Cited by 324 · cited 1×
“The reasons for the latter are unknown and may involve either hormone-dependent events such as an increase in free fatty acids and reorganization of cardiolipin in the IMM (32, 33) or altered regulation of electron transfer to CYP11A1 affecting its enzymatic activity (15, 34).”
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Han, S., Zhao, L., Luo, J., Shi, C., Yao, C., Ji, Z., Xu, J., Xu, S., Tian, R., Zhi, E., et al. (2025) · Reproductive Biology and Endocrinology · doi:10.1186/s12958-025-01389-w · Cited by 4
“LH induces a rapid synthesis of StAR which helps to transfer cholesterol crossing mitochondrial membranes to increase testosterone [35, 36].”
Daňhelovská, T., Zdražilová, L., Štufková, H., Vanišová, M., Volfová, N., Křížová, J., Kuda, O., Sládková, J., & Tesařová, M. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22147270 · Cited by 4
“The group led by V. Papadopoulos described a multiprotein complex (transduceosome) formed of StAR, VDAC1, TSPO, ACBD3, PKARIα (type I PKA), ATAD3, and CYP11A1 (mito cyt P450) [6,18].”
BackgroundGarza, S., Sottas, C. M., Gukasyan, H. J., & Papadopoulos, V. (2024) · Frontiers in Toxicology · doi:10.3389/ftox.2024.1357857 · Cited by 5
Self-citationCanine Mammary Tumours (CMTs) exploit mitochondrial cholesterol for aggressive reprogramming
Hardy, L., Kannan, B., Rigon, M., Benton-Hawthorn, G., Previdelli, R. L., Reichler, I. M., Guscetti, F., Kowalewski, M. P., & Campanella, M. (2024) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2024.167546 · Cited by 3
Chemali, L. E., Boutary, S., Liu, S., Liu, G. J., Middleton, R. J., Banati, R. B., Bahrenberg, G., Rupprecht, R., Schumacher, M., & Massaad-Massade, L. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25137327 · Cited by 3
“The efficacy of TSPO ligands is difficult to predict from their affinities and pharmacokinetics, possibly because TSPO is part of a mitochondrial multi-protein complex [32,51–53].”
BackgroundKawahara, Y., Mitsui, K., Niwa, T., Morimoto, N., Kawaharada, S., & Katsumata, S. (2018) · Neurogastroenterology & Motility · doi:10.1111/nmo.13425 · Cited by 3
Kennedy, B. E., Charman, M., & Karten, B. (2017) · Methods in molecular biology · doi:10.1007/978-1-4939-6875-6_12 · Cited by 4
Rousseau, D. L. (2019) · Journal of Medicine and Therapeutics · doi:10.15761/jmt.1000139 · Cited by 3
“The most recent studies have lightened up a new and very interesting hypothesis developed by Papadopoulos and colleagues and deeply analysed [78-80].”
BackgroundLeydig Cells: Fetal to Aged Testes
Culty, M., Papadopoulos, V., & Zirkin, B. R. (2018) · Elsevier eBooks · doi:10.1016/b978-0-12-801238-3.64360-x · Cited by 3
Self-citationMartin, L. J. (2025) · Steroids · doi:10.1016/j.steroids.2025.109735 · Cited by 2
Regulation of Adrenal Steroidogenesis
Pihlajoki, M., Heikinheimo, M., & Wilson, D. B. (2017) · Contemporary Endocrinology · doi:10.1007/978-3-319-62470-9_2 · Cited by 3
Cell Biology and Regulation of Adult and Aging Leydig Cell Steroidogenesis
Papadopoulos, V., Garza, S., & Zirkin, B. R. (2025) · Springer eBooks · doi:10.1007/978-3-031-96376-6_4 · Cited by 2
Self-citationSteroidogenic Acute Regulatory Protein (StAR) and Atherogenesis
Graham, A., Borthwick, F., & Taylor, J. M. W. (2014) · Springer eBooks · doi:10.1007/978-1-4939-1112-7_5 · Cited by 2
“[50] described a dynamic 800 kDa bioactive protein complex in steroidogenic cells, spanning the outer and inner mitochondrial membranes, consisting of TSPO, VDAC, cytochrome P450 side chain cleavage enzyme (CYP11A1), ATPase family AAA domain-containing protein 3 A (ASTAD3A) and optic atrophy type 1 proteins, but not A…”
BackgroundLeydig Cell Development and Aging in the Brown Norway Rat
Zirkin, B. R., Chen, H., & Papadopoulos, V. (2018) · Elsevier eBooks · doi:10.1016/b978-0-12-811353-0.00062-2 · Cited by 2
Self-citationCongenital Lipoid Adrenal Hyperplasia
Miller, W. L. (2014) · Springer eBooks · doi:10.1007/978-1-4939-1112-7_4 · Cited by 3
Mitochondria form contact sites with the nucleus to couple pro-survival retrograde responsePreprint
Desai, R., East, D. A., Hardy, L., Crosby, J., Rigon, M., Faccenda, D., Alvarez, M. S., Singh, A., Mainenti, M., Hussey, L. K., et al. (2018) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/445411 · Cited by 2
Functional interpretation of ATAD3A variants in neuro-mitochondrial phenotypesPreprint
Yap, Z. Y., Park, Y., Wortmann, S. B., Gunning, A. C., Lee, S., Duraine, L., Wilichowski, E., Wilson, K., Mayr, J. A., Wagner, M., et al. (2020) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2020.10.05.318519 · Cited by 2
Transcriptome analysis of atad3-null zebrafish embryos elucidates possible disease mechanisms
Ezer, S., Ronin, N., Yanovsky‐Dagan, S., Rotem‐Bamberger, S., Halstuk, O., Wexler, Y., Ben-Moshe, Z., Plaschkes, I., Benyamini, H., Saada, A., et al. (2025) · Orphanet Journal of Rare Diseases · doi:10.1186/s13023-025-03709-0 · Cited by 1
“ATAD3A is also integral to cholesterol metabolism [6].”
Couty, N., Ramé, C., Berthet, L., Chevaleyre, C., Péchoux, C., Froment, P., & Dupont, J. (2026) · Poultry Science · doi:10.1016/j.psj.2026.106850 · Cited by 2
“In addition, proper mitochondrial morphology and membrane organization are essential for the assembly and activity of steroidogenic enzyme complexes (Rone et al., 2012).”
Asimaki, K., van de Lest, C. H. A., Wubbolts, R., Jansen, J. W. A., Helms, J. B., Aardema, H., van Duursen, M. B. M., & Gadella, B. M. (2026) · Biology of Reproduction · doi:10.1093/biolre/ioag119 · Cited by 1
“The mobilized cholesterol could be directly imported into the mitochondria, via LD-mitochondrial contact sites and the action of cholesterol transporters (e.g., StAR), leading to progesterone production [ 52].”
Thirumurugan, A., Ravi, S., & Annamalai, A. (2026) · The Journal of Steroid Biochemistry and Molecular Biology · doi:10.1016/j.jsbmb.2026.107088 · Cited by 1
Rousseau, D. L. (2016) · Journal of Genetics and Genome Research · doi:10.23937/2378-3648/1410027 · Cited by 1
A lei de almotaçaria e a política económica de Afonso III
Viana, M. (2013) · Portuguese National Funding Agency for Science, Research and Technology (RCAAP Project by FCT) · Cited by 1
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Fernandes, T., Domingues, M. R., Pereira, C., & Moreira, P. I. (2023) · Elsevier eBooks · doi:10.1016/b978-0-443-19247-0.00012-6 · Cited by 1
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Rousseau, D. L. (2016) · Journal of Clinical and Molecular Endocrinology
Bindra, S., McGill, M. A., Triplett, M. K., Tyagi, A., Thaker, P. H., Dahmoush, L., Goodheart, M. J., Ogden, T., Owusu-Ansah, E., Karan, K. R., et al. (2021) · Research Square · doi:10.21203/rs.3.rs-246331/v1
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“(2) We identified mechanisms of cholesterol import into mitochondria and showed that TSPO is a high-affinity cholesteroland drug-binding protein, serves as an anchor for signaling molecules targeted to mitochondria, and controls mitochondrial function as well as the rate of steroid formation in rodents and humans [20,…”
BackgroundMulti-omic analysis of the aging mouse brain
Kluever, V. (2021) · eDiss (Georg-August-Universität Göttingen) · doi:10.53846/goediss-9022
Poderoso, C., Castillo, A. F., Mele, P. G., Maloberti, P. M., & Podesta, E. J. (2017) · Springer eBooks · doi:10.1007/978-3-319-67199-4_101896
Poderoso, C., Castillo, A. F., Mele, P. G., Maloberti, P. M., & Podesta, E. J. (2016) · Springer eBooks · doi:10.1007/978-1-4614-6438-9_101896-1
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Fairley, L. H. (2022) · DR-NTU (Nanyang Technological University) · doi:10.32657/10356/160865
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Gaudó, P., de Tomás-Mateo, E., Garrido-Pérez, N., Santana, A., Ruiz‐Pesini, E., Montoya, J., & Bayona‐Bafaluy, M. P. (2023) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2023.12.006
Wetzel, C. H., Bader, S. M., Jahner, T., Doerfelt, A., Melchner, D., Cardon, I., Siegmund, H. I., Brochhausen, C., Rupprecht, R., & Milenkovic, V. M. (2024) · Research Square · doi:10.21203/rs.3.rs-4024118/v1
Additional file 1 of Functional interpretation of ATAD3A variants in neuro-mitochondrial phenotypes
Yap, Z. Y., Park, Y. H., Wortmann, S. B., Gunning, A. C., Ezer, S., Lee, S., Duraine, L., Wilichowski, E., Wilson, K., Mayr, J. A., et al. (2021) · Figshare · doi:10.6084/m9.figshare.14404057
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Li, L., Sheikhpour, E., Zirkin, B. R., & Papadopoulos, V. (2025) · Elsevier eBooks · doi:10.1016/b978-0-443-21477-6.00417-x
Self-citationAdditional file 2 of Functional interpretation of ATAD3A variants in neuro-mitochondrial phenotypes
Yap, Z. Y., Park, Y. H., Wortmann, S. B., Gunning, A. C., Ezer, S., Lee, S., Duraine, L., Wilichowski, E., Wilson, K., Mayr, J. A., et al. (2021) · Figshare · doi:10.6084/m9.figshare.14404060
Iatmanen-Harbi, S. (2014) · theses.fr (ABES) · doi:10.70675/5616c185z2443z4e3bz9af0zcfb6141df5ac
Marginedas-Freixa, I. (2017) · theses.fr (ABES) · doi:10.70675/c493d7f5zc4b3z4debzb54fza7d98f55233f
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Tifoun, N. (2021) · theses.fr (ABES) · doi:10.70675/19d943dcz4ccfz40b3z8e0ez5530fe24e55f
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Metadata
- Authors
- Rone, M. B., Midzak, A. S., Issop, L., Rammouz, G., Jagannathan, S., Fan, J., Ye, X., Blonder, J., Veenstra, T., & Papadopoulos, V.
- Affiliations
- Research Institute of the McGill University Health Centre (CA)
- National Cancer Institute (US)
- Corresponding author
- Papadopoulos, Vassilios
- Venue
- Molecular Endocrinology
- Publisher
- The Endocrine Society
- Published
- 2012-11-01
- Volume
- 26
- Issue
- 11
- Pages
- 1868-1882
- ISSN
- 0888-8809 (ISSN-L)
- 1944-9917
- PMC
- PMC5416962
- OpenAlex
- W2103518814
- Cited by
- 247
- References
- 41
- Citations by year
- 2026: 6 · 2025: 12 · 2024: 15 · 2023: 12 · 2022: 13 · 2021: 28 · 2020: 28 · 2019: 20 · 2018: 11 · 2017: 17 · 2016: 27 · 2015: 17 · 2014: 23 · 2013: 16 · 2012: 2
- FWCI
- 7.46
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Molecular Endocrinology (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- McGill University
- McGill University Health Centre
- National Institutes of Health
- Canadian Institutes of Health Research (MOP102647, TGF36110)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Physical Sciences › Chemistry › Organic Chemistry › Steroid Chemistry and Biochemistry
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Lipid Membrane Structure and Behavior
- Keywords
- steroidogenesis, CYP11A1, translocator protein (TSPO), voltage-dependent anion channel, ATAD3A, steroidogenic acute regulatory protein, mitochondrial outer membrane, inner mitochondrial membrane, cholesterol transport, Leydig cells
- MeSH terms
- Steroidogenic Acute Regulatory Protein, Animals, Biological Transport, Cholesterol, Cholesterol Side-Chain Cleavage Enzyme, Chorionic Gonadotropin, Hormones, Leydig Cells, Male, Models, Biological, Molecular Weight, Oxazines, Phosphoproteins, Mass Spectrometry, Mitochondrial Proteins, Multiprotein Complexes, Mitochondrial Membranes, Mice, Native Polyacrylamide Gel Electrophoresis
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