Biology subjects

Ma, P.

Publications and source records attributed to Ma, P..

3 recordsLinked to original sources

bioRxiv2026

Mitochondrial transfer mediates metabolic communication between beta cells and islet macrophages

Pancreatic islet macrophages support islet homeostasis and adapt their metabolic program in response to environmental cues, including beta cell released factors. Intercellular mitochondrial transfer is a biological process that modulates cellular responses. To test whether beta cells, which are strongly secretory, transfer mitochondria to islet macrophages, we generated mice with beta cell-specific expression of mitochondrial GFP (PhAMfloxIns1Cre). We demonstrate that beta cells transfer mitochondria to islet macrophages in vivo and in vitro. Diabetogenic stressors did not alter the frequency of mitochondrial transfer and macrophages containing beta cell-derived GFP exhibit increased protein synthesis rates. RNA-seq identified upregulation of activity-regulated cytoskeleton associated protein (Arc) in macrophages receiving beta cell-derived mitochondria, while disruption of actin cytoskeleton dynamics prevented mitochondrial transfer. Together, these findings identify mitochondrial transfer as a previously unrecognized mechanism of beta cell-macrophage communication that may contribute to islet homeostasis and immune regulation.

cell biology↗

bioRxiv2018

Structural and biochemical characterization on the cognate and heterologous interactions of the MazEF-mt9 TA system

The toxin-antitoxin (TA) modules widely exist in bacteria, and their activities are associated with the persister phenotype of the pathogen Mycobacterium tuberculosis (M. tb). M. tb causes Tuberculosis, a contagious and severe airborne disease. There are ten MazEF TA systems in M. tb, which play important roles in stress adaptation. How the antitoxins antagonize toxins in M. tb or how the ten TA systems crosstalk to each other are of interests, but the detailed molecular mechanisms are largely unclear. MazEF-mt9 is a unique member among the MazEF families due to its tRNase activity, which is usually carried out by the VapC family toxins. Here we present the cocrystal structure of the MazEF-mt9 complex at 2.7 [A]. By characterizing the association mode between the TA pairs through various characterization techniques, we found that MazF-mt9 not only bound its cognate antitoxin, but also the non-cognate antitoxin MazE-mt1, a phenomenon that could be also observed in vivo. Based on our structural and biochemical work, we proposed that the cognate and heterologous interactions among different TA systems work together to relieve MazF-mt9s toxicity to M. tb cells, which may facilitate their adaptation to the stressful conditions encountered during host infection.\n\nIMPORTANCETuberculosis (TB) is one of the most severe contagious diseases. Caused by Mycobacterium tuberculosis (M. tb), it poses a serious threat to human health. Additionally, TB is difficult to cure because of the multipledrug-resistant (MDR) and extensively drug-resistant (XDR) M. tb strains. Toxin-antitoxin (TA) systems have been discovered to widely exist in prokaryotic organisms with diverse roles, normally composed of a pair of molecules that antagonize each other. M. tb has ten MazEF systems, and some of them have been proved to be directly associated with the genesis of persisters and drug-resistance of M. tb. We here report the MazEF-mt9 complex structure, and thoroughly characterized the interactions between MazF-mt9 with MazEs within or outside the MazEF-mt9 family. Our study not only revealed the crosstalks between TA families and its significance to M. tb survival but also offers insights into potential anti-TB drug design.

biochemistry↗

bioRxiv2016

The Aquarius/EMB-4 helicase licenses co-transcriptional gene silencing

Small RNAs (sRNAs) play an ancient role in genome defence against transposable elements. In animals, plants and fungi small RNAs guide Argonaute proteins to nascent RNA transcripts to induce co-transcriptional gene silencing. In animals the link between small RNA pathways and the transcriptional machinery remains unclear. Here we show that the Caenorhabditis elegans germline Argonaute HRDE-1 physically interacts with the conserved RNA helicase Aquarius/EMB-4. We demonstrate that the Aquarius/EMB-4 helicase activity is required to initiate small RNA-induced co-transcriptional gene silencing. HRDE-1 and Aquarius/EMB-4 are required to silence the transcription of overlapping sets of transposable elements. Surprisingly, removal of introns from a small RNA pathway target abolishes the requirement for Aquarius/EMB-4, but not HRDE-1, for gene silencing. We conclude that the Aquarius/EMB-4 helicase activity allows HRDE-1/sRNA complexes to efficiently engage nascent RNA transcripts - in competition with the general RNA processing machinery. We postulate that Aquarius/EMB-4 facilitates the surveillance of the nascent transcriptome to detect and silence transposable elements through small RNA pathways.

molecular biology↗