Surveying the mitochondrial proteome

Author(s):  
Dominic Winter ◽  
Thomas Becker
2021 ◽  
Vol 22 (15) ◽  
pp. 8325
Author(s):  
Paola Zanfardino ◽  
Stefano Doccini ◽  
Filippo M. Santorelli ◽  
Vittoria Petruzzella

Oxidative phosphorylation (OxPhos) is the basic function of mitochondria, although the landscape of mitochondrial functions is continuously growing to include more aspects of cellular homeostasis. Thanks to the application of -omics technologies to the study of the OxPhos system, novel features emerge from the cataloging of novel proteins as mitochondrial thus adding details to the mitochondrial proteome and defining novel metabolic cellular interrelations, especially in the human brain. We focussed on the diversity of bioenergetics demand and different aspects of mitochondrial structure, functions, and dysfunction in the brain. Definition such as ‘mitoexome’, ‘mitoproteome’ and ‘mitointeractome’ have entered the field of ‘mitochondrial medicine’. In this context, we reviewed several genetic defects that hamper the last step of aerobic metabolism, mostly involving the nervous tissue as one of the most prominent energy-dependent tissues and, as consequence, as a primary target of mitochondrial dysfunction. The dual genetic origin of the OxPhos complexes is one of the reasons for the complexity of the genotype-phenotype correlation when facing human diseases associated with mitochondrial defects. Such complexity clinically manifests with extremely heterogeneous symptoms, ranging from organ-specific to multisystemic dysfunction with different clinical courses. Finally, we briefly discuss the future directions of the multi-omics study of human brain disorders.


1998 ◽  
Vol 19 (6) ◽  
pp. 1006-1014 ◽  
Author(s):  
Thierry Rabilloud ◽  
Sylvie Kieffer ◽  
Vincent Procaccio ◽  
Mathilde Louwagie ◽  
Paul L. Courchesne ◽  
...  

Diabetes ◽  
2009 ◽  
Vol 58 (9) ◽  
pp. 1986-1997 ◽  
Author(s):  
H. Bugger ◽  
D. Chen ◽  
C. Riehle ◽  
J. Soto ◽  
H. A. Theobald ◽  
...  

Toxicon ◽  
2018 ◽  
Vol 156 ◽  
pp. 34-40 ◽  
Author(s):  
Mei Wang ◽  
Yu Chen ◽  
Zhen Guo ◽  
Changcheng Yang ◽  
Jiaomei Qi ◽  
...  

Cells ◽  
2018 ◽  
Vol 7 (10) ◽  
pp. 172 ◽  
Author(s):  
Braulio Vargas Möller-Hergt ◽  
Andreas Carlström ◽  
Tamara Suhm ◽  
Martin Ott

The mitochondrial proteome contains proteins from two different genetic systems. Proteins are either synthesized in the cytosol and imported into the different compartments of the organelle or directly produced in the mitochondrial matrix. To ensure proteostasis, proteins are monitored by the mitochondrial quality control system, which will degrade non-native polypeptides. Defective mitochondrial membrane proteins are degraded by membrane-bound AAA-proteases. These proteases are regulated by factors promoting protein turnover or preventing their degradation. Here we determined genetic interactions between the mitoribosome receptors Mrx15 and Mba1 with the quality control system. We show that simultaneous absence of Mrx15 and the regulators of the i-AAA protease Mgr1 and Mgr3 provokes respiratory deficiency. Surprisingly, mutants lacking Mrx15 were more tolerant against proteotoxic stress. Furthermore, yeast cells became hypersensitive against proteotoxic stress upon deletion of MBA1. Contrary to Mrx15, Mba1 cooperates with the regulators of the m-AAA and i-AAA proteases. Taken together, these results suggest that membrane protein insertion and mitochondrial AAA-proteases are functionally coupled, possibly reflecting an early quality control step during mitochondrial protein synthesis.


Author(s):  
Federica Marini ◽  
Victor Corasolla Carregari ◽  
Viviana Greco ◽  
Maurizio Ronci ◽  
Federica Iavarone ◽  
...  

2018 ◽  
Author(s):  
Caroline Fecher ◽  
Laura Trovò ◽  
Stephan A. Müller ◽  
Nicolas Snaidero ◽  
Jennifer Wettmarshausen ◽  
...  

AbstractMitochondria vary in morphology and function in different tissues, however little is known about their molecular diversity among cell types. To investigate mitochondrial diversity in vivo, we developed an efficient protocol to isolate cell type-specific mitochondria based on a new MitoTag mouse. We profiled the mitochondrial proteome of three major neural cell types in cerebellum and identified a substantial number of differential mitochondrial markers for these cell types in mice and humans. Based on predictions from these proteomes, we demonstrate that astrocytic mitochondria metabolize long-chain fatty acids more efficiently than neurons. Moreover, we identified Rmdn3 as a major determinant of ER-mitochondria proximity in Purkinje cells. Our novel approach enables exploring mitochondrial diversity on the functional and molecular level in many in vivo contexts.


2021 ◽  
Vol 22 (21) ◽  
pp. 11606
Author(s):  
Brad Ebanks ◽  
Ying Wang ◽  
Gunjan Katyal ◽  
Chloe Sargent ◽  
Thomas L. Ingram ◽  
...  

Ageing is a major risk factor for many of the most prevalent diseases, including neurodegenerative diseases, cancer, and heart disease. As the global population continues to age, behavioural interventions that can promote healthy ageing will improve quality of life and relieve the socioeconomic burden that comes with an aged society. Exercise is recognised as an effective intervention against many diseases of ageing, but we do not know the stage in an individual’s lifetime at which exercise is most effective at promoting healthy ageing, and whether or not it has a direct effect on lifespan. We exercised w1118 Drosophila melanogaster, investigating the effects of sex and group size at different stages of their lifetime, and recorded their lifespan. Climbing scores at 30 days were measured to record differences in fitness in response to exercise. We also assessed the mitochondrial proteome of w1118 Drosophila that had been exercised for one week, alongside mitochondrial respiration measured using high-resolution respirometry, to determine changes in mitochondrial physiology in response to exercise. We found that age-targeted exercise interventions improved the lifespan of both male and female Drosophila, and grouped males exercised in late life had improved climbing scores when compared with those exercised throughout their entire lifespan. The proteins of the electron transport chain were significantly upregulated in expression after one week of exercise, and complex-II-linked respiration was significantly increased in exercised Drosophila. Taken together, our findings provide a basis to test specific proteins, and complex II of the respiratory chain, as important effectors of exercise-induced healthy ageing.


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