Non-cell-autonomous regulation of germline proteostasis by insulin/IGF-1 signaling-induced dietary peptide uptake via PEPT-1.

Gametogenesis involves active protein synthesis and is proposed to rely on proteostasis. Our previous work in C. elegans indicates that germline development requires coordinated activities of insulin/IGF-1 signaling (IIS) and HSF-1, the central regulator of the heat shock response. However, the downstream mechanisms were not identified. Here, we show that depletion of HSF-1 from germ cells impairs chaperone gene expression, causing protein degradation and aggregation and, consequently, reduced fecundity and gamete quality. Conversely, reduced IIS confers germ cell resilience to HSF-1 depletion-induced protein folding defects and various proteotoxic stresses. Surprisingly, this effect was not mediated by an enhanced stress response, which underlies longevity in low IIS conditions, but by reduced ribosome biogenesis and translation rate. We found that IIS activates the expression of intestinal peptide transporter PEPT-1 by alleviating its repression by FOXO/DAF-16, allowing dietary proteins to be efficiently incorporated into an amino acid pool that fuels germline protein synthesis. Our data suggest this non-cell-autonomous pathway is critical for proteostasis regulation during gametogenesis.

Cardiac Manifestations of Hemochromatosis.

Cardiac hemochromatosis, a consequence of primary or secondary iron-overload conditions, poses a threat to patient health, leading to cardiomyopathy and heart failure. This review aims to compile comprehensive information on cardiac hemochromatosis, elucidating its pathophysiology, clinical presentation, diagnosis, and management strategies. Primary and secondary hemochromatosis, genetic and acquired forms, can result in cardiotoxicity by means of iron dysregulation. Diagnostic tools, including biochemical markers, electrocardiography, echocardiography, and magnetic resonance imaging (MRI), are utilized for early detection as well as long-term monitoring post-treatment. For treatment options, phlebotomy is the standard, but for some patients (such as those with anemia), chelation therapy is an alternative option. Other potential therapies include erythrocytapheresis, calcium channel blockers, and hepcidin-targeted approaches, for which more research is needed to understand cardiac function benefits. With the onset of cardiac symptoms, patient health rapidly deteriorates. Thus, timely intervention to mitigate associated morbidity and mortality by means of screening can promote and prolong patient survival.