MITGETS Doctoral Candidates share the recent publications
Mitochondria are vital organelles present in almost all eukaryotic cells and are involved in the primary cellular metabolic pathways. Mutations affecting mitochondrial function lead to a wide range of diseases, many of which remain poorly understood. The foundation of proper mitochondrial function begins with the maintenance of the mitochondrial genome, whose expression plays a crucial role in the synthesis and assembly of protein subunits essential to the oxidative phosphorylation system. This system enables mitochondria to produce energy and serve as the so-called “powerhouses of the cells.” To raise awareness during World Mitochondrial Disease Week, DC05 and DC06 are sharing their contributions as researchers in mitochondrial gene expression and maintenance systems, summarized in two review papers published this summer.
MITGEST DC05, Giulia Santonocento contributed to the recent review titled “RNA degradation in human mitochondria: the journey is not finished.” This paper provides an overview of mitochondrial genome expression, with a particular focus on mitochondrial RNA decay and surveillance mechanisms, which are essential for shaping the final mitochondrial transcriptome. The latter can be thought of as an instruction manual that, once followed, leads to the assembly of the key components of the mitochondrion, specifically the protein subunits mentioned above. Transcription of the human mitochondrial genome results in both sense protein-encoding mRNAs (mt-mRNAs) and a significant amount of antisense noncoding RNAs (as-ncRNAs). Although most protein-encoding mRNAs are synthesized at similar rates, their final levels can vary. This means that, after the synthesis, additional steps are required to ensure the correct amount of each class of mt-mRNAs produced. On the other hand, no specific functional role has been identified for antisense non-coding RNAs (as-ncRNAs). In fact, their excessive presence can lead to abnormal and dangerous conditions. For this reason, their levels are kept very low, thanks to the action of a key player: the mitochondrial degradosome, which is composed of two essential parts—a component called SUV3 and another called PNPase. In this review, we focus on and delve deeper into these important aspects of mitochondrial biology. Moreover, since, despite significant efforts, these mechanisms are still not fully understood, we also highlight the open questions in the field and the intriguing hypotheses that could lead to new avenues for research.
Similarly, MITGEST DC06, Daria Kovalchuk investigated some mechanisms regarding the step following transcription, i.e. the translation of mitochondrial-encoded proteins. In particular, she contributed to the recent review titled “Decoding the Enigma of Translation Termination in Human Mitochondria.” This paper sheds light on key advances and ongoing challenges related to the termination phase of the mitochondrial translation cycle, focusing on the roles of two specific mitochondrial release factors, mtRF1 and mtRF1a. Notably, mutations in mtRF1a have been linked to mitochondrial dysfunction, including impairments in oxidative phosphorylation and energy metabolism. Despite significant progress, several critical questions remain unanswered. These include the varying cellular impacts on COX1 and ND6 transcripts in mtRF1 knockout models, as well as the possibility of stopping codon read-through events in mitochondria. The review also explores the evolutionary significance of these two release factors, hypothesizing that it may serve a dual function or act as a backup mechanism in protein translation for species lacking AGA/AGG codons. This review, led by the Joanna Rorbach group, calls for further experimental research to unravel the complexities of mitochondrial translation and enhance our understanding of mitochondrial diseases.
Both of these works underscore the importance of continued research into mitochondrial gene expression and maintenance. Understanding these intricate processes is vital not only for unravelling the mysteries of mitochondrial dysfunction but also for developing potential therapeutic strategies to treat mitochondrial-related diseases. As researchers, we remain committed to advancing knowledge in this field and hope that our contributions inspire further exploration in this crucial area of biomedical science.
