The Lysosome and Intracellular Signalling.

In addition to being the terminal degradative compartment of the cell's endocytic and autophagic pathways, the lysosome is a multifunctional signalling hub integrating the cell's response to nutrient status and growth factor/hormone signalling. The cytosolic surface of the limiting membrane of the lysosome is the site of activation of the multiprotein complex mammalian target of rapamycin complex 1 (mTORC1), which phosphorylates numerous cell growth-related substrates, including transcription factor EB (TFEB). Under conditions in which mTORC1 is inhibited including starvation, TFEB becomes dephosphorylated and translocates to the nucleus where it functions as a master regulator of lysosome biogenesis. The signalling role of lysosomes is not limited to this pathway. They act as an intracellular Ca2+ store, which can release Ca2+ into the cytosol for both local effects on membrane fusion and pleiotropic effects within the cell. The relationship and crosstalk between the lysosomal and endoplasmic reticulum (ER) Ca2+ stores play a role in shaping intracellular Ca2+ signalling. Lysosomes also perform other signalling functions, which are discussed. Current views of the lysosomal compartment recognize its dynamic nature. It includes endolysosomes, autolysosome and storage lysosomes that are constantly engaged in fusion/fission events and lysosome regeneration. How signalling is affected by individual lysosomal organelles being at different stages of these processes and/or at different sites within the cell is poorly understood, but is discussed

"Pierre Hadot et les “exercices spirituels”: Quel modèle pour la philosophie bouddhique tardive?"

In uncovering the practical, institutional and quasi-religious dimensions of ancient Western philosophical traditions, the French historian Pierre Hadot has paved the way for a renewed interest in philosophy as a spiritual phenomenon. As stressed in Hadot's many works, ancient and early medieval philosophy should not be viewed as a discourse committed to systematic presentation of doctrines and arguments, but rather as a way of life entailing spiritual exercises (discursive as well as non discursive) that mobilizes the philosopher's whole personality. Leading scholars in the field of Buddhist studies have argued recently that Pierre Hadot's ideas may provide a fruitful model in attempts at understanding at least some late Buddhist literary productions (mainly of the so-called epistemological school) as philosophy. Promising as this approach may be (and I think it is), its relevance with regard to authors like Dharmakirti and Santaraksita depends mainly on one's interpretation of the Buddhist epistemologists' self-understanding. No less importantly, resorting to Pierre Hadot's ideas challenges Buddhist studies' awareness of issues such as the location and sectarian (i.e., disciplinary) affiliation of these thinkers, or their commitment to traditional Buddhist “meditative” practices (asubhabhavana, krtsnayatana, etc.). The present essay does not aim at criticising this approach, but to draw attention to the kind of historical knowledge buddhologists should search for in order to apply this model to Buddhist epistemological texts in a still more stimulating and rewarding way

On a Hitherto Neglected Text Against Buddhist Personalism: Mahāyānasūtrālaṅkāra 18.92–103 and its Bhāṣya

According to the Chinese pilgrims Xuanzang and Yijing, the Sāṃmitīya sect of Buddhism, an offshoot of the Vātsīputrīya sect, had become by far the most important among the non-Mahāyānist denominations of the northern half of India by the turn of the 7th century CE. Now, the Sāṃmitīyas were famous for professing a personalist doctrine (pudgalavāda) that singled them out as “heretics” and triggered off vehement criticism on the part of their “coreligionists.” Whereas only a few Sāṃmitīya works have survived down to us in Chinese translation, most of their opponents’ tracts have been preserved either in Sanskrit or in Tibetan translation, the most celebrated ones being those of Vasubandhu, Candrakīrti and Kamalaśīla. However, one of the earliest extant Yogācāra sources, the Mahāyānasūtrālaṅkāra(bhāṣya), dedicates a section of respectable length to the critique of Buddhist personalism. The present essay provides this neglected early testimony with an introduction, an annotated translation, and text-critical notes

"Caste" et philosophie bouddhique. Continuité de quelques arguments bouddhiques contre le traitement réaliste des dénominations sociales

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