Lysosome/vacuole-mediated intracellular degradation pathways, collectively known as autophagy, play crucial roles in the maintenance and regulation of various cellular functions. However, little is known about the relationship between different modes of autophagy. In the budding yeast Saccharomyces cerevisiae, nitrogen starvation triggers both macronucleophagy and micronucleophagy, in which nuclear components are degraded via macroautophagy and microautophagy, respectively. We previously revealed that Atg39-mediated macronucleophagy is important for cell survival under nitrogen starvation; however, the underlying mechanism remains unknown. Here, we reveal that defective Atg39-mediated macronucleophagy leads to the hyperactivation of micronucleophagy, resulting in the excessive transport of various nuclear components into the vacuole. Micronucleophagy occurs at the nucleus–vacuole junction (NVJ). We show that nuclear membrane proteins localized to the NVJ, including Nvj1, which is responsible for micronucleophagy, are degraded via macronucleophagy. Therefore, defective Atg39-mediated macronucleophagy results in the accumulation of Nvj1, which contributes to micronucleophagy enhancement. Blocking micronucleophagy almost completely suppresses cell death caused by the absence of Atg39, whereas enhanced micronucleophagy correlates with death in Atg39-mutant cells under nitrogen starvation. These results suggest that macronucleophagy modulates micronucleophagy in order to prevent the excess removal of nuclear components, thereby maintaining nuclear and cellular homeostasis during nitrogen starvation.

溶酶体/液泡介导的细胞内降解途径，统称为自噬，在维持和调节各种细胞功能中起着至关重要的作用。然而，人们对不同自噬模式之间的关系知之甚少。在出芽酵母酿酒酵母中，氮饥饿触发巨核自噬和微核自噬，其中核成分分别通过巨自噬和微自噬降解。我们之前揭示了 Atg39 介导的大核自噬对氮饥饿下的细胞存活很重要;然而，其潜在机制仍不清楚。在这里，我们揭示了有缺陷的 Atg39 介导的大核自噬导致微核自噬过度激活，导致各种核成分过度转运到液泡中。微核自噬发生在细胞核-液泡连接处 （NVJ）。我们表明，定位于 NVJ 的核膜蛋白，包括负责微核自噬的 Nvj1，通过大核自噬降解。因此，Atg39 介导的有缺陷的大自噬导致 Nvj1 的积累，这有助于微核自噬增强。阻断微核自噬几乎完全抑制了由 Atg39 缺失引起的细胞死亡，而增强的微核自噬与氮饥饿下 Atg39 突变细胞的死亡相关。这些结果表明，巨核自噬调节微核自噬以防止核成分的过度去除，从而在氮饥饿期间维持核和细胞稳态。