Article
Biology
Holly C. Ford, William J. Allen, Goncalo C. Pereira, Xia Liu, Mark Simon Dillingham, Ian Collinson
Summary: This article describes the import process of mitochondrial proteins and the research progress in understanding its mechanisms. Using a newly developed assay based on split NanoLuc luciferase, researchers found that the size and net charge of pre-sequences influence the import process, which is driven by the transmembrane potential and ATP hydrolysis. The study also revealed the functional differences between the two membranes involved in the import process.
Article
Multidisciplinary Sciences
Qiang Wang, Zeyuan Guan, Liangbo Qi, Jinjin Zhuang, Chen Wang, Sixing Hong, Ling Yan, Yan Wu, Xiaoqian Cao, Jianbo Cao, Junjie Yan, Tingting Zou, Zhu Liu, Delin Zhang, Chuangye Yan, Ping Yin
Summary: Sam37 stabilizes mature Tom40 mainly through electrostatic interactions, facilitating subsequent TOM assembly. These results support the b barrel switching model and offer structural insights into the assembly and release of b barrel complexes.
Article
Biochemistry & Molecular Biology
Xueyin Zhou, Yuqi Yang, Guopeng Wang, Shanshan Wang, Dongjie Sun, Xiaomin Ou, Yuke Lian, Long Li
Summary: This study reports the mechanism of mitochondrial protein import via the pre-sequence pathway through the TOM-TIM23 supercomplex. Cryo-EM and structural analyses reveal that polypeptide substrates pass through the TOM complex and enter the TIM23 complex via a negatively charged entrance and a central hydrophobic region.
NATURE STRUCTURAL & MOLECULAR BIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Chetana Tamadaddi, Vinay Sagar, Amit K. Verma, Fathima Afsal, Chandan Sahi
Summary: Our study reveals that selective interactions between JDPs in plant mitochondria may determine their functional specificity and provide resilience to protein import processes in mitochondria.
PLANT MOLECULAR BIOLOGY
(2021)
Article
Multidisciplinary Sciences
Ridhima Gomkale, Andreas Linden, Piotr Neumann, Alexander Benjamin Schendzielorz, Stefan Stoldt, Olexandr Dybkov, Markus Kilisch, Christian Schulz, Luis Daniel Cruz-Zaragoza, Blanche Schwappach, Ralf Ficner, Stefan Jakobs, Henning Urlaub, Peter Rehling
Summary: The TOM and TIM23 complexes facilitate the transport of nuclear-encoded proteins into the mitochondrial matrix. By using a stalled client protein, the authors purified the translocation supercomplex and gained insights into the TOM-TIM23 interface and the mechanism of protein handover from the TOM to the TIM23 complex.
NATURE COMMUNICATIONS
(2021)
Article
Biology
Shuo Wang, Lukas Findeisen, Sebastian Leptihn, Mark I. Wallace, Marcel Hoerning, Stephan Nussberger
Summary: Wang et al. used single-molecule measurements to uncover a potentially new mechanosensitive functionality of mitochondrial TOM core complexes. They found that TOM-CC switches reversibly between different ion permeability states associated with protein diffusion. This behavior is explained by the mechanical binding of TOM-CC to a hydrogel and the opening and closing of beta-barrel pores.
COMMUNICATIONS BIOLOGY
(2022)
Article
Plant Sciences
Mabel Gill-Hille, Andre Wang, Monika W. Murcha
Summary: The PAM complex is essential for the import and assembly of most mitochondrial proteome. In this study, we analyzed the localization of PAM complex orthologues in Arabidopsis and found that Pam16 is exclusively targeted to mitochondria while Pam18 orthologues can be targeted to both mitochondria and plastids, similar to the interacting partner proteins Tim15 and Mge1.
FRONTIERS IN PLANT SCIENCE
(2022)
Article
Multidisciplinary Sciences
Laura F. Fielden, Jakob D. Busch, Sandra G. Merkt, Iniyan Ganesan, Conny Steiert, Hanna B. Hasselblatt, Jon V. Busto, Christophe Wirth, Nicole Zufall, Sibylle Jungbluth, Katja Noll, Julia M. Dung, Ludmila Butenko, Karina von der Malsburg, Hans-Georg Koch, Carola Hunte, Martin van der Laan, Nils Wiedemann
Summary: The presequence translocase of the mitochondrial inner membrane (TIM23) is the major route for importing nuclear-encoded proteins into mitochondria. Tim17, a subunit of TIM23, interacts with preproteins in the matrix or inner membrane for protein translocation. The negative charges in Tim17 initiate the translocation mechanism and release the preproteins into the inner membrane.
Article
Multidisciplinary Sciences
Agalya Periasamy, Naomi Mitchell, Olga Zaytseva, Arjun S. Chahal, Jiamin Zhao, Peter M. Colman, Leonie M. Quinn, Jacqueline M. Gulbis
Summary: Intronic polymorphic variants of TOMM40 that increase TOMM40 mRNA expression are strongly linked to late onset Alzheimer's Disease. Using the fruit fly Drosophila melanogaster as a model, researchers found that an excess of the Tom40 protein, a homologue of hTomm40, in mitochondria leads to caspase-dependent cell death and degeneration of neuronal eye tissue. The degeneration is dependent on the presence of assembled TOM components, suggesting that an increase in assembled TOM triggers apoptosis and degeneration. Increased Tom40 expression also results in the upregulation and association of a mitochondrial oxidative stress biomarker, DmHsp22, which is linked to extended lifespan. This research provides insights into the potential causal pathway from TOMM40 polymorphisms to neurodegenerative disease.
SCIENTIFIC REPORTS
(2022)
Article
Biochemistry & Molecular Biology
Tejashree Pradip Waingankar, Patrick D'Silva
Summary: Mitochondrial protein translocation is a complex process regulated by dedicated translocases on the outer and inner membranes. Magmas, a J-like protein subunit of the translocase of the inner membrane 23, can regulate human protein import by forming heterodimers with J-proteins. Additional Magmas variants in humans play a significant role in maximizing protein import under familial-linked pathological conditions.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2021)
Article
Biology
Marcel G. Genge, Shalini Roy Chowdhury, Vit Dohnalek, Kaori Yunoki, Takashi Hirashima, Toshiya Endo, Pavel Dolezal, Dejana Mokranjac
Summary: This study reveals the coordination mechanism of translocation of proteins across mitochondrial membranes, and finds that both the core and PBD domains of Tim50 play essential roles in this process.
LIFE SCIENCE ALLIANCE
(2023)
Review
Cardiac & Cardiovascular Systems
Fujie Zhao, Ming-Hui Zou
Summary: Mitochondria play essential roles in cellular functions and various diseases, including heart disease. The protein import machinery of mitochondria is crucial for these functions and warrants further research for potential therapeutic strategies in heart disease.
FRONTIERS IN CARDIOVASCULAR MEDICINE
(2021)
Review
Biochemistry & Molecular Biology
Ulfat Mohd Hanif Sayyed, Radhakrishnan Mahalakshmi
Summary: The article discusses the unique properties of the human mitochondrial outer membrane and the importance of the TOM complex. It highlights the recent research progress and the potential impact on alleviating human diseases.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2022)
Review
Physiology
Marcel G. Genge, Dejana Mokranjac
Summary: The majority of mitochondrial proteins are synthesized in the cytosol and contain specific mitochondrial targeting signals. These signals, such as presequences, help guide the proteins to the mitochondrial matrix with the assistance of TOM and TIM23 complexes in the outer and inner membranes. The TOM and TIM23 complexes interact in the intermembrane space, facilitating the transfer of presequences and precursor proteins from the outer to the inner mitochondrial membrane.
FRONTIERS IN PHYSIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Naintara Jain, Ridhima Gomkale, Olaf Bernhard, Peter Rehling, Luis Daniel Cruz-Zaragoza
Summary: Mitochondria play a crucial role in cellular energy production and metabolism, and errors in mitochondrial protein import can lead to metabolic disorders. This study establishes a fluorescence-based import assay to analyze protein import into mitochondria, offering the advantage of quantifying import with high sensitivity. The assay can be adapted to a screening-compatible format and used to monitor the assembly of the F1F0 ATP synthase in purified mitochondria.