Sorting of exclusive mitochondrial proteins from the Mitoproteome database

Abstract

World Wide Web and scientific literature record information regarding several organelles and mitochondria is not an exception. However, currently mitochondrial databases also provide information about non-mitochondrial proteins. As on date, there is no way to know the exclusive mitochondrial proteins. It is crucial to know the exclusively mitochondrial proteins, present in mitochondria but absent elsewhere. In this work, by analysis of available databases, we have provided a list of exclusively mitochondrial proteins known as on date.

Background

Mitochondria research is a pivot of current research in life sciences. It is unraveling several facts which revolutionize humans understanding about biology. At present, several databases are available dealing functional annotation of proteins and genes with respect to organelle including mitochondria.

Localization of mitochondrial proteins is annotated already (Rath et al. 2021). It has been demonstrated that 99% mitochondrial proteins are nuclear genome encoded. There are only 13 proteins in the mitochondria that are encoded by mitochondrial genome. Different guiding factors like mitochondrial targeting sequence (MTS), translocase of outer membrane (TOM) complex, etc., are established for mitochondrial protein translocation (Nicolas et al. 2019). Another study has reported that hydrophobic membrane proteins encoded by mitochondrial genome are synthesized in endoplasmic reticulum, while nuclear-encoded proteins are synthesized in cytoplasm (Bjorkholm et al. 2015). So, coordination between mitochondrial and nuclear genomes is necessary for mitochondrial biogenesis at normal and stressed conditions (Lionaki et al. 2016). Very recently, an RNA-binding protein, Clustered mitochondria homolog (CLUH) is identified as mitochondrial protein translation regulator in cytoplasm (Hemono et al. 2022).

Mitochondrial proteins or genes perform numerous and diverse functions in apoptosis, energy conversation, heat production, homeostasis, cancer, ageing, cell signaling and death pathways (Pfanner et al. 2019; Lin et al. 2022). Therefore, mitochondrial protein/gene sequence databases and annotation system are crucial for mitochondrial researchers. Some databases record details about proteins location, function, etc., where mitochondrial proteins are present (The Human Protein Atlas 2022; Helix Mitochondrial DNA Database—Available for Research Analysis-Helix Population Genomics 2022; Organelle Genome Resources 2022). However, it is difficult to figure out which proteins are exclusive mitochondrial and which are not. In this context, we have sorted exclusively mitochondrial proteins from existing database (MitoProteome, OMIM, UniProt, The Human Protein Atlas).

To the Editor,

The Mitoproteome database

Mitoproteome, human mitochondrial protein database is freely available at http://www.mitoproteome.org/. It contains known mitochondrial proteins obtained either from mass spectrometric analysis of highly purified human heart mitochondria or retrieved from other publicly available databases (Cotter 2004). Other human mitochondrial protein databases do not have the complete information about all mitochondrial and nuclear-encoded proteins (Ravichandran et al. 2016). Databases dealing with mitochondrial proteins primarily highlight mitochondrial and nuclear-encoded proteins and localization in mitochondria.

Whether the Mitoproteome database represents exclusively mitochondrial proteins?

In the Mitoproteome database, we have observed that some of the mentioned proteins were exclusively mitochondrial, while others can be found at other organelles also. In this context, we had searched the literature and various databases like The Human protein Atlas, UniProt, HGNC database and OMIM database to classify the proteins on the aforementioned basis and made a separate table for exclusively mitochondrial and non-mitochondrial proteins/genes. The NCBI Protein Blast was used to sort mitochondrial proteins/genes that showed 100% sequence similarity to humans and were listed as exclusive mitochondrial proteins/genes of humans (Table 1). Some common examples of exclusive human mitochondrial proteins are citrate synthase, superoxide dismutase 2, succinate dehydrogenase complex, etc. The remaining proteins/genes that show sequence similarity to proteins of other organelles are listed as non-exclusive mitochondrial genes/proteins (Table 2). Examples of non-exclusive mitochondrial proteins are fumarate hydratase, glutathione reductase, sestrin 2, etc.

Table 1 List of exclusive mitochondrial proteins

Table 2 List of proteins that are not present exclusively in mitochondria

In some situations, knowledge of exclusive proteins is crucial. For example, cyanide is lethal as it inhibits cytochrome c oxidase, a mitochondrial ETC protein. It inhibits an exclusive mitochondrial function needed for maintenance of life process. We are continuously getting exposed to several chemicals, and such exposure is definitely having effect on mitochondrial function. As an example, aluminum phosphide (rice or wheat pill) which induces phosphine exposure acts as mitochondrial poison (Yadav et al. 2021). We do not know entirely with which mitochondrial proteins it interacts. This is because we do not have complete information about exclusive mitochondrial proteins. We believe that data generated here will pave the path in such direction. Further a protein whose information is mentioned in a mitochondrial database so far generated is not always an exclusive mitochondrial protein, but it can be misunderstood so from the name of the database. For example (Table 2, Sr. No.2), acyl-CoA synthetase long-chain family member 1 is a protein whose information is recorded in Mitoproteome database; but it is also found in peroxisomes. So, the information generated in the present study will help the researchers to get rid of such confusion.

Sorting of exclusive mitochondrial proteins is necessary because these interaction networks have various roles in maintaining the normal physiology of cells (Pourahmad et al. 2015). Dysfunction of mitochondrial proteins/genes has been associated with neurological, liver, oxygen deficiency, inborn and metabolic diseases (Javadov et al. 2020). Therefore, knowledge about mitochondrial proteins/genes is essential to understand disease progression, mitochondrial evolution, functional protein–protein interaction network, cancer prevention, stem cell and regeneration biology (Chakrabarty et al. 2018). We believe that if such information is available with the Mitoproteome database, it will help the researchers.

Conclusions

This work documents the list of exclusively mitochondrial proteins known as on date. With the progress of human knowledge, the list needs to be updated and revised.